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Background: The multitude of metabolites generated by physiological processes in the body can serve as valuable biomarkers for many clinical purposes. They can provide a window into relevant metabolic pathways for health and disease, as well as be candidate therapeutic targets. A subset of these metabolites generated in the human body are volatile, known as volatile organic compounds (VOCs), which can be detected in exhaled breath. These can diffuse from their point of origin throughout the body into the bloodstream and exchange into the air in the lungs. For this reason, breath VOC analysis has become a focus of biomedical research hoping to translate new useful biomarkers by taking advantage of the non-invasive nature of breath sampling, as well as the rapid rate of collection over short periods of time that can occur. Despite the promise of breath analysis as an additional platform for metabolomic analysis, no VOC breath biomarkers have successfully been implemented into a clinical setting as of the time of this review. Aim of review: This review aims to summarize the progress made to address the major methodological challenges, including standardization, that have historically limited the translation of breath VOC biomarkers into the clinic. We highlight what steps can be taken to improve these issues within new and ongoing breath research to promote the successful development of the VOCs in breath as a robust source of candidate biomarkers. We also highlight key recent papers across select fields, critically reviewing the progress made in the past few years to advance breath research. Key scientific concepts of review: VOCs are a set of metabolites that can be sampled in exhaled breath to act as advantageous biomarkers in a variety of clinical contexts. [ABSTRACT FROM AUTHOR]

As a supplemental technique for disease diagnosis, expelled breath monitoring is becoming extremely prevalent. Nevertheless, because of the significant number of factors that must be considered, researchers are forced to create new algorithms for accurate data interpretations. In our study, a novel noninvasive breath biomarkers-based diabetic detection strategy is introduced by upcoming three main processes "pre-processing, feature extraction and diabetes detection". Raw data (breath signal) are initially pre-processed via data normalization to increase acquired breath signal quality. Most important features, such as "Improved empirical wavelet functions (IEWF), empirical mode decomposition (EMD), local mean decomposition (LMD), continuous wavelet transform (CWT) method, and entropy-based feature," are extracted from the pre-processed data. These attributes are fused together and are subsequently used to train the ensemble of classifiers in the diabetes detection stage. An ensemble of classifiers, including an "optimized quantum deep neural network (QDNN), a convolutional neural network (CNN), and a recurrent neural network (RNN)", is used to depict the diabetes detection phase. The CNN and RNN are trained using the retrieved fused features. The optimized QDNN receives the output of the CNN and RNN. The final detected result is provided by the optimized QDNN. A unique hybrid optimization model, Archimedes Principle with Enhanced Honey Badger Exploitation (APEHBE) algorithm, that combines the Archimedes Optimization Algorithm (ArchOA) and the Honey Badger Algorithm (HBA) is used to fine-tune the weight of QDNN. The effectiveness of the anticipated model is then verified by a comparison analysis. [ABSTRACT FROM AUTHOR]

In this paper, an innovative device with gas remote-sensing capability is proposed, which is based on the interaction between magnetic nanoparticles and gases associated with exhaled breath biomarkers that can have a metabolic origin. Magnetite (Fe₃O₄) nanoparticles of around 30 nm have been used. The gas molecules adsorbed on surface modulate the magnetization of the nanoparticles and magnetostatic surface spin waves (MSSW) propagated on an yttrium iron garnet (YIG) thin film are used to detect this modulation by the induced frequency shift. The optimization of the remote gas sensor has been carried out through simulations of a magnetic model. Simulations show the feasibility of developing a high-performance remote sensor by encapsulating the nanostructures in a polytetrafluoroethylene (PTFE) tube and detecting part per million changes in their magnetization. The results show the possibility of developing new, inexpensive, reusable, contactless magnetic gas sensors employing spin waves as transductor. The developed sensor shows a high sensitivity and selectivity to concentrations as low as 50 ppm of different breath biomarkers.

Rapid screening of tuberculosis by evaluation of associated volatile organic biomarkers in breath is a promising technology that is significantly faster and more convenient than traditional sputum culture tests. Methyl nicotinate (MN) and methyl p-anisate (MPA) have been isolated as potential biomarkers for mycobacterium tuberculosis and have been found in the breath of patients with active pulmonary tuberculosis. A novel approach to detection of these biomarkers in liquid droplets (e.g. from breath condensate) using inexpensive screen-printed electrodes is presented. Previous modelling studies suggest that these biomarkers complex with certain transition metals of particular valence state. This interaction can be exploited by mixing the biomarker sample into an electroactive solution (EAS) containing the functional metal ion and observing the change electrochemically. The study focuses on low biomarker concentrations, determined to be clinically relevant based on preliminary GC-MS studies of the levels found in patient breath. It was found that both the cyclic voltammogram and square wave voltammogram of copper(II) change significantly when as little as 0.1 mM MN is added to the solution, with analysis times of less than 2 min. Copper(II) exhibits three separate peaks during square wave voltammetry. The location and area of each peak are affected differently as the concentration of MN increases, suggesting a reaction with specific oxidation states of the metal. In this way, a "fingerprint" method can be used to identify biomarkers once their known interaction is established.

Respiratory surveillance is the process whereby a group of exposed workers are regularly tested (or screened) for those lung diseases which occur as a result of a specific work exposure. Surveillance is performed by assessing various measures of biological or pathological processes (or biomarkers) for change over time. These traditionally include questionnaires, lung physiological assessments (especially spirometry), and imaging. Early detection of pathological processes or disease can enable removal of a worker from a potentially harmful exposure at an early stage. In this article, we summarize the physiological biomarkers currently used for respiratory surveillance, while commenting on differences in interpretative strategies between different professional groups. We also briefly review the many new techniques which are currently being assessed for respiratory surveillance in prospective research studies and which are likely to significantly broaden and enhance this field in the near future. [ABSTRACT FROM AUTHOR]

Breath composition analysis is a fast and non-invasive alternative to commonly used methods of detecting lung cancer, such as biopsy. One issue in the study of breath composition is the availability of appropriate sampling and sample-preparation methods that are able to fully capture the gas and droplet phases of exhaled breath. In this article, we detail the application of a filter-incorporated needle-trap device (NTD) to capture gaseous compounds and droplets in breath samples. In addition, a thin-film microextraction method was also employed to conduct extractions from only the gas phase. In comparing the NTD (total concentration) and TFME (free concentration) results, it is possible to obtain a more comprehensive view of the sample, as this approach captures both the free and droplet-bound concentrations, which can in turn provide a better characterization of the cancer. Furthermore, the developed devices were applied for the on-site sampling of lung cancer patients. The complete interpretation of the results and their relationship to the state of the disease and patient health status requires a large cohort of patients and considerable medical expertise; therefore, this study focuses on method development and the application of the proposed device for fast and sensitive on-site detection of biomarkers in patients.

The unique characteristics of 2-dimensional hetero structure offers efficient gas sensing with high selectivity to identify gases from the interference gases which is quite difficult. In the present work, ZnO: SnO2Nano composite clusters (NCC) is prepared. A resistive metal oxide volatile organic compound (VOC) gas sensor is fabricated with nullifying the effect of humidity by increasing temperature optimally. A single-step SOL-GEL (SG) synthesis is used to prepare ZnO: SnO2 NCC with maximum Zn/Sn molar concentration ratio of 3. The morphological studies through Scanning Electron Microscopy (SEM), electrical properties due to oxygen vacancies and energy band variations of Nanocomposite are measured. The enhancement of gas sensor sensitivity due to highly mesoporous nature of the composite is observed. From the findings, the abundant mesopores in the range of 2 nm-14 nm and specific surface area of 54.2 m² g−1 with the average crystal size of 14.236 nm, and polar surface area of the composite 25.9651Åis achieved. When compared to bare ZnO and SnO2 gas sensors, the present gas sensor offers the higher selectivity with enhanced performance due to the mesoporous structure. Fast repeatability rate of 2200 sec at 350ºC to ethanol is attained and the overall selectivity of the sensor increased twice as 2.085. The NCC compound is tested firstly with micro organisms such as B. subtilis (B. S), Bacillus cereus (B. C), B. coagulans (B. C), Pseudonymous auriginosa (P. A) are considered for antimicrobial activity. From the findings, zinc stannate compound showed good efficacy towards B. cereus Gram positive and P.A gram-negative. A bacterial growth is arrested highly with B. cereus. [ABSTRACT FROM AUTHOR]

Preservation of the breath sample integrity during storage and transport is one of the biggest challenges in off-line exhaled breath gas analysis. In this context, adsorbent tubes are frequently used as storage containers for use with analytical methods employing gas chromatography with mass spectrometric detection. The key objective of this short communication is to provide data on the recovery of selected breath volatiles from Tenax ® TA adsorbent tubes that were stored at -80 °C for up to 90 d. For this purpose, an Owlstone Medical's ReCIVA ® Breath Sampler was used for exhaled breath collection. The following fifteen compounds, selected to cover a range of chemical properties, were monitored for their stability: isoprene, n-heptane, n-nonane, toluene, p-cymene, allyl methyl sulfide, 1-(methylthio)-propane, 1-(methylthio)-1-propene, α -pinene, DL-limonene, β -pinene, γ -terpinene, 2-pentanone, acetoin and 2,3 butanedione. All compounds, but one (acetoin), were found to be stable during the first 4 weeks of storage (recovery within ± 2 × RSD). Furthermore, n-nonane was stable during the whole of the investigated period., (Creative Commons Attribution license.)

The analysis of exhaled breath has attracted considerable interest for use in disease diagnosis and for monitoring treatments. Mass spectrometry (MS)-based approaches have been proven to be powerful analytical tools for breath analysis in clinical applications such as disease research, diagnosis, and monitoring. This review highlights MS methodologies as potential clinical tools in diagnosing human diseases. Different breath sampling methods and MS methods for breath analysis are reviewed, emphasizing their features, advantages, and limitations. Breath biomarkers from different diseases are summarized, describing their specificity, sensitivity, and drawbacks. The future perspectives and challenges on further development of MS-based breath diagnostics are discussed. [Display omitted] • Recent advances in breath analysis by mass spectrometry are reviewed. • Clinical applications of breath diagnostics are summarized. • Challenges of breath biomarkers for disease diagnosis are highlighted. • Future perspectives on breath diagnostics in clinical applications are discussed. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the clinical value of exhaled nitric oxide (NO) for diagnosing lung cancer patients by using a relatively large sample. An online and near-real-time ringdown exhaled NO analyzer calibrated by an electrochemical sensor at clinical was used for breath analysis. A total of 740 breath samples from 284 healthy control subjects (H) and 456 lung cancer patients (LC) were collected. The recorded data included exhaled NO, medications taken within the last half month, demographics, fasting status and smoking status. The LC had a significantly higher level of exhaled NO than the H (H: 21.0 ± 12.1 ppb vs. LC: 34.1 ± 17.2 ppb). The area under the receiver operating characteristic curve for exhaled NO predicting LC and H was 0.728 (sensitivity was 0.798; specificity was 0.55). There was no significant difference in exhaled NO level between groups divided by different types of LC, tumor node metastasis (TNM) stage, sex, smoking status, age, body mass index (BMI) or fasting status. Exhaled NO level alone is not a useful clinical tool for identifying lung cancer, but it should be considered when developing a diagnosis model of lung cancer by using breath analysis.

Assessment and treatment of postoperative pain can be challenging as objective examination techniques to detect and quantify pain are lacking. We aimed to investigate changes of exhaled volatile organic compounds (VOCs) in patients with postoperative pain before and after treatment with opioid analgesics. In an observational study in 20 postoperative patients, we monitored for postoperative pain, hemodynamic parameters, and catecholamines before and during treatment. VOCs in the patients were determined by direct real-time proton transfer reaction time-of-flight mass spectrometry prior (0 min) and after piritramide application (15 min as well as 30 min). Cardiovascular variables changed and norepinephrine levels decreased during treatment. The VOCs acetonitrile (p = 0.002), benzopyran (p = 0.004), benzene (p < 0.001), hexenal (p = < 0.001), 1-butanethiol (p = 0.004), methanethiol (p < 0.001), ethanol (p = 0.003), and propanol (p = < 0.001) changed significantly over time. Patients with Numeric Rating Scale (NRS) < 4 showed a significantly lower concentration of hexenal compared to patients with NRS > 4 at the time points 15 min (45.0 vs. 385.3 ncps, p = 0.047) and 30 min (38.3 vs. 334.6 ncps, p = 0.039). Breath analysis can provide additional information for noninvasive monitoring for analgesic treatment in postoperative patients.

Two-dimensional (2D) nanomaterials such as graphene, transition metal dichalcogenides, black phosphorus, metal-organic framework, MXenes, and metal oxide nanosheets, etc. are being envisioned as the next-generation sensing materials for extremely diversified sensing applications and nano-electronics owing to their excellent electrical, mechanical, physicochemical and optical properties. These 2D nanomaterials-based semiconductor gas sensors have unlocked a new horizon in the field of non-invasive detection of diseases, through the identification of the biomarkers in human breath. This review paper focuses on the different attributes of 2D nanomaterials, their sensing mechanism, and various methods utilized in the selective detection of biomarker molecules. Functionalization of 2D nanomaterials to fabricate semiconductor-based gas sensors to distinguish between a healthy patient and a patient with the disease are discussed. Wherever relevant, limitations of the contemporary methods and future outlook have also been delineated. [Display omitted] • A compact knowledge on the properties, applications of 2D nano-structures in breath sensing. • Essential sensing mechanism of 2D nanomaterials based breath sensors is discoursed to get better insight. • Analytical performances of various sensing platforms were categorically presented in tables and compared. • Wherever relevant, limitations of current methodologies and future outlook have also been delineated. [ABSTRACT FROM AUTHOR]

Breath-composition analysis is a well-established, non-invasive method for early disease diagnosis and investigating exposure history. However, this analytical approach is hampered by the aerosol nature of breath samples and/or low concentrations of volatile organic compounds. Conventionally, two separate methods have been applied to study gas phase and breath droplets, although these approaches are expensive and time-consuming. To address this issue, for the first time a needle-trap device packed with Carboxen, which served as a sorbent for the extraction of volatile analytes from the gas-phase, and electrospun polyacrylonitrile filter, which used to capture breath aerosol was applied to breath characterization. The performance of the developed device was subsequently compared to that of Carboxen-loaded thin-film microextraction, which was employed for the first time to extract free gas-phase components. Both methods were optimized, validated, and applied for the screening of breath samples obtained from volunteers. Obtained figures of merits are as follows: limits of detection (0.01–0.2 ng mL−1), recovery (81–108%) and repeatability (<13%). To investigate the effect of droplets, breath samples acquired with and without a face mask were compared. While both methods yielded similar results for the breath samples obtained with the mask, the needle-trap device was able to provide higher concentrations of volatile organic compounds for the samples acquired without a mask due to its enhanced ability to trap droplets. Additionally, tests were also conducted to investigate breath composition after accidental exposure to chemicals. The results of these tests revealed that polar compounds tended to partition to breath droplets and were eliminated from the body more quickly, while non-polar compounds tended to remain in the gas phase and were eliminated at a slower rate. [Display omitted] • A thermally resistant porous filter was prepared from electrospun polyacrylonitrile. • The developed filter and Carboxen particles were packed in the needle-trap device. • Filter-incorporated needle-trap device was applied for study of breath aerosol. • Breath vapor was investigated with Carboxen embedded thin-film microextraction. • The combined data from both methods can be used for comprehensive breath monitoring. [ABSTRACT FROM AUTHOR]

Abstract: The diagnosis of asymptomatic cirrhosis in patients with liver disease is of importance to start screening for complications in due time. Liver biopsy is neither sensitive nor practical enough to be used as a frequent follow-up test in patients with chronic liver disease. The volatile organic compounds present in exhaled breath offer the possibility of exploring internal physiologic and pathologic process in a non invasive way. This study examined whether a specific pattern of biomarkers can be found in breath samples of patients with cirrhosis. To this aim samples of alveolar breath from patients with cirrhosis and healthy volunteers were analyzed using gas chromatography–mass spectrometry. When linear discriminant analysis was used to search for a model(s)/pattern of compounds characteristic for liver cirrhosis, 24 models of 8 independent compounds could distinguish between the groups. The sensitivity and specificity (between 82% and 88%, and 96% and 100%, respectively) of the models suggest that a specific pattern of breath biomarkers can be found in patients with cirrhosis, which may allow detecting this complication of chronic liver disease in an early stage. [Copyright &y& Elsevier]

Abstract: This paper compares three methods for estimating renal function, as tested in rats. Acute renal failure (ARF) was induced via a 60-min bilateral renal artery clamp in 8 Sprague–Dawley rats and renal function was monitored for 1 week post-surgery. A two-compartment model was developed for estimating glomerular filtration via a bolus injection of a radio-labelled inulin tracer, and was compared with an estimated creatinine clearance method, modified using the Cockcroft–Gault equation for rats. These two methods were compared with selected ion flow tube-mass spectrometry (SIFT-MS) monitoring of breath analytes. Determination of renal function via SIFT-MS is desirable since results are available non-invasively and in real time. Relative decreases in renal function show very good correlation between all 3 methods (R 2 =0.84, 0.91 and 0.72 for breath-inulin, inulin-creatinine, and breath-creatinine correlations, respectively), and indicate good promise for fast, non-invasive determination of renal function via breath testing. [Copyright &y& Elsevier]

Different compounds have been reported as biomarkers of a smoking habit, but, to date, there is no appropriate biomarker for tobacco-related exposure because the proposed chemicals seem to be nonspecific or they are only appropriate for short-term exposure. Moreover, conventional sampling methodologies require an invasive method because blood or urine samples are required. The use of a microtrap system coupled to gas chromatography–mass spectrometry analysis has been found to be very effective for the noninvasive analysis of volatile organic compounds in breath samples. The levels of benzene, 2,5-dimethylfuran, toluene, o-xylene, and m- p-xylene have been analyzed in breath samples obtained from 204 volunteers (100 smokers, 104 nonsmokers; 147 females, 57 males; ages 16 to 53 years). 2,5-Dimethylfuran was always below the limit of detection (0.005 ppbv) in the nonsmoker population and always detected in smokers independently of the smoking habits. Benzene was only an effective biomarker for medium and heavy smokers, and its level was affected by smoking habits. Regarding the levels of xylenes and toluene, they were only different in heavy smokers and after short-term exposure. The results obtained suggest that 2,5-dimethylfuran is a specific breath biomarker of smoking status independently of the smoking habits (e.g., short- and long-term exposure, light and heavy consumption), and so this compound might be useful as a biomarker of smoking exposure. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Accurate assessment of dietary macronutrients intake is critical for the effective management of multiple diseases, such as obesity, diabetes, cardiovascular disease, metabolic disease, and cancer. Conventional self-reporting method is burdensome, inaccurate, and often biased. Though blood analysis and breath analysis can provide evidence-based information, they are either invasive or subject to human errors. Here we reported a wearable transdermal volatile biomarkers detection system based on novel colorimetric sensing technology for dietary macronutrients intake assessment. This technique quantifies the emission rates of transdermal volatile biomarkers via a gradient-based colorimetric array sensor (GCAS). The optical system of the GCAS device tracks the localized color development associated with the chemical reaction between the volatile biomarkers and the porous sensing probes, and determines the biomarkers emission rates through image processing algorithms. The localized chemical reaction and the image-based signal processing also make the GCAS capable for multiplexed detection of multiple analytes simultaneously. The GCAS sensor has been applied for transdermal acetone detection on 5 subjects in a keto diet intervention. The study indicates that the transdermal acetone increases after the subjects consuming keto diets and it decreases to basal level after intaking carb-rich diets. The transdermal acetone response from the GCAS sensor correlates well with breath acetone concentration in the range between 0 and 40 ppm and the correlation factor (R2) is as high as 0.8877. This method provides a noninvasive, low-cost, and wearable tool for assessing dietary macronutrients intake outside of lab or hospital settings. It could be widely applied in disease management, weight control, and nutrition management. • A wearable biosensing system for transdermal biomarkers detection. • Noninvasive, low-cost, and wearable tool for assessing dietary macronutrients. • The gradient-based colorimetric array capable for multiplexed detection of multiple analytes simultaneously and continuously. [ABSTRACT FROM AUTHOR]

Assessment and treatment of postoperative pain can be challenging as objective examination techniques to detect and quantify pain are lacking. We aimed to investigate changes of exhaled volatile organic compounds (VOCs) in patients with postoperative pain before and after treatment with opioid analgesics. In an observational study in 20 postoperative patients, we monitored for postoperative pain, hemodynamic parameters, and catecholamines before and during treatment. VOCs in the patients were determined by direct real-time proton transfer reaction time-of-flight mass spectrometry prior (0 min) and after piritramide application (15 min as well as 30 min). Cardiovascular variables changed and norepinephrine levels decreased during treatment. The VOCs acetonitrile (<0.001), acetaldehyde (p = 0.002), benzopyran (p = 0.004), benzene (p < 0.001), hexenal (p = < 0.001), 1-butanethiol (p = 0.004), methanethiol (p < 0.001), ethanol (p = 0.003), and propanol (p = < 0.001) changed significantly over time. Patients with Numeric Rating Scale (NRS) < 4 showed a significantly lower concentration of hexenal compared to patients with NRS > 4 at the time points 15 min (45.0 vs. 385.3 ncps, p = 0.047) and 30 min (38.3 vs. 334.6 ncps, p = 0.039). Breath analysis can provide additional information for noninvasive monitoring for analgesic treatment in postoperative patients. [ABSTRACT FROM AUTHOR]

Unlabelled: Great interest of scientific community is observed recently over non-invasive tests methods dedicated to diagnose disease states using biomarkers. The ability to detect these substances in the human breath can provide valuable information about disorder of biochemical processes in the body. Breath analysis is non-invasive, painless and can provide a quick answer about the existence of the disease. In addition, the sampling process is carried out comfortably for both the patient and the medical staff., Aim: The aim of the study was to present opportunity of application the optoelectronic methods for screening tests in medical diagnostics. The results of the researches carried out at the Institute of Experimental Physics, Department of Physics UW and at the Institute of Optoelectronics MUT are presented., Materials and Methods: For the detection of methane and ammonia in breath the Multipass Spectroscopic Absorption Cells (MUPASS ) were used. In the case of nitric oxide and ethane observation, Cavity Enhanced Absorption Spectroscopy (CEAS) was applied. During the investigation modern tunable and sophisticated infrared radiation sources were used: single mode diode lasers (for CH4, NH3 detection), quantum cascade laser (NO sensing), and optical parametric generator (PG711/DFG) for ethane measurements. The investigations of developed sensors were conducted with use of reference samples of biomarkers, which were prepared with gas standards generator 491M from KIN-TEK company., Results: Experiments showed that sensitivities of the sensors are suitable for human breath analyzing. In case of methane sensor, the detection limit (sensitivity) of ~ 0.1 ppm was obtained. This value is significantly lower than the upper limit of methane concentration in the breath of healthy humans (10 ppm). Therefore, our system well satisfies the requirements for diseases screening (e.g. intestines diseases ) and for methane monitoring in healthy human breath. Ammonia sensor is characterized with linear response in the concentration range higher than 1 ppm. The upper limit of ammonia concentration in healthy human breath is approx. 2 ppm, so this system is well suited for the determination of disease states (e.g. liver diseases). During the observation of nitrogen oxide the detection limit of 30 ppb was obtained. According to the ATS recommendation such NO detection limit is sufficient to monitor people's health state and for the detection of respiratory diseases like asthma or chronic bronchitis. For ethane detection with a wavelength of 3.348 microns the detection limit of 20 ppb was obtained., Conclusions: Developed sensors are characterized by high sensitivity (ppb-level) and high selectivity, simple and fast measurement procedure. Therefore, they can be applied as medical screening tools enabling biomarkers detection in exhaled air at the molecular level., (© 2015 MEDPRESS.)