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Standardisation of breath sampling is important for application of breath analysis in clinical settings. By studying the effect of room airing on indoor and breath analytes and by generating time series of room air with different sampling intervals we sought to get further insights into room air metabolism, to detect the relevance of exogenous VOCs and to make conclusions about their consideration for the interpretation of exhaled breath. Room air and exhaled breath of a healthy subject were analysed before and after room airing. Furthermore a time series of room air with doors and windows closed was taken over 84 h by an automatic sampling every 180 min. A second times series studied room air analytes over 70 h with samples taken every 16.5 min. For breath and room air measurements an IMS coupled to a multi-capillary column (IMS/MCC) [Bio-Scout® - BS Pentan-2-one [107-87-9] – Dimer; Hexan-1-al [66-25-1]; Pentan-2-one [107-87-9]) – Monomer showed high intensities in the room air and exhaled breath. They were significantly but not equally reduced by room airing. The time series about 84 h showed a time dependent decrease of analytes (limonen-monomer and -dimer; Decamethylcylopentasiloxane, Butan-1-ol, Butan-1-ol) as well as increase (Pentan-2-one [107-87-9] – Dimer). Shorter sampling intervals exhibited circadian variations of analyte concentrations for many analytes. Breath sampling in the morning needs room airing before starting. Then the variation of the intensity of indoor analytes can be kept small. The time series of indoor analytes show, that their intensities have a different behaviour, with time dependent declines, constant increases and circadian variations, dependent on room airing. This has implications on the breath sampling procedure and the intrepretation of exhaled breath.

ACS Sensors, 4 (2), ISSN:2379-3694

In this report, we present a post hoc analysis from two observational cohorts, comparing the global breath volatile profile captured when using polymer sampling bags (mixed breath) versus Bio-VOC™ (alveolar breath). The cohorts were originally designed to characterize the breath volatile profiles of Malawian children with and without uncomplicated falciparum malaria. Children aged 3–15 years were recruited from ambulatory pediatric centers in Lilongwe, Malawi. Breath sampling was carried out two months apart (one study using a Bio-VOC™ and the second using sampling bags), and all samples were analyzed by gas chromatography/mass spectrometry. The efficacy of breath collection was assessed by quantifying levels of two high prevalence breath compounds, acetone and isoprene, as well as determining the overall number of breath compounds collected and their abundance. We found that the mean number of volatiles detected using sampling bags was substantially higher than when using the Bio-VOC™ (137 vs. 47). Breath collection by Bio-VOC™ also yielded reduced levels of endogenous breath volatiles, isoprene and acetone, even after breath volume correction. This suggests that the Bio-VOC™ dilutes the volatiles and introduces dead air or ambient air. Our results suggest that sampling bags are better suited for biomarker discovery and untargeted search of volatiles in pediatric populations, as evidenced by superior breath volatile detection.

Background Asthma and COPD continue to cause considerable diagnostic and treatment stratification challenges. Volatile organic compounds (VOCs) have been proposed as feasible diagnostic and monitoring biomarkers in airway diseases. Aims To 1) conduct a systematic review evaluating the diagnostic accuracy of VOCs in diagnosing airway diseases; 2) understand the relationship between reported VOCs and biomarkers of type-2 inflammation; 3) assess the standardisation of reporting according to STARD and TRIPOD criteria; 4) review current methods of breath sampling and analysis. Methods A PRISMA-oriented systematic search was conducted (January 1997 to December 2020). Search terms included: “asthma”, “volatile organic compound(s)”, “VOC” and “COPD”. Two independent reviewers examined the extracted titles against review objectives. Results 44 full-text papers were included; 40/44 studies were cross-sectional and four studies were interventional in design; 17/44 studies used sensor-array technologies (e.g. eNose). Cross-study comparison was not possible across identified studies due to the heterogeneity in design. The commonest airway diseases differentiating VOCs belonged to carbonyl-containing classes (i.e. aldehydes, esters and ketones) and hydrocarbons (i.e. alkanes and alkenes). Although individual markers that are associated with clinical biomarkers of type-2 inflammation were recognised (i.e. ethane and 3,7-dimethylnonane for asthma and α-methylstyrene and decane for COPD), these were not consistently identified across studies. Only 3/44 reported following STARD or TRIPOD criteria for diagnostic accuracy and multivariate reporting, respectively. Conclusions Breath VOCs show promise as diagnostic biomarkers of airway diseases and for type-2 inflammation profiling. However, future studies should focus on transparent reporting of diagnostic accuracy and multivariate models and continue to focus on chemical identification of volatile metabolites., VOCs show promise as noninvasive biomarkers for airway disease diagnosis, anchored to biomarkers of type-2 inflammation https://bit.ly/3utL3sx

Exhaled breath analysis is a promising new diagnostic tool, but currently no standardised method for sampling is available in mechanically ventilated patients. We compared two breath sampling methods, first using an artificial ventilator circuit, then in "real life"in mechanically ventilated patients on the intensive care unit. In the laboratory circuit, a 24-component synthetic-breath volatile organic compound (VOC) mixture was injected into the system as air was sampled: (A) through a port on the exhalation limb of the circuit and (B) through a closed endo-bronchial suction catheter. Sorbent tubes were used to collect samples for analysis by thermal desorption-gas chromatography-mass spectrometry. Realistic mechanical ventilation rates and breath pressure-volume loops were established and method detection limits (MDLs) were calculated for all VOCs. Higher yields of VOCs were retrieved using the closed suction catheter; however, for several VOCs MDLs were compromised due to the background signal associated with plastic and rubber components in the catheters. Different brands of suction catheter were compared. Exhaled VOC data from 40 patient samples collected at two sites were then used to calculate the proportion of data analysed above the MDL. The relative performance of the two methods differed depending on the VOC under study and both methods showed sensitivity towards different exhaled VOCs. Furthermore, method performance differed depending on recruitment site, as the centres were equipped with different brands of respiratory equipment, an important consideration for the design of multicentre studies investigating exhaled VOCs in mechanically ventilated patients.

Exhaled breath contains hundreds of volatile organic compounds (VOCs) which offer the potential for diagnosing and monitoring a wide range of diseases. As the breath research field has grown, sampling and analytical practices have become highly varied between groups. Standardisation would allow meta-analyses of data from multiple studies and greater confidence in published results. Washout of VOCs from ingestion into the blood and subsequently breath could provide data for an initial assessment of inter-group performance. The Peppermint Initiative has been formed to address this task of standardisation. In the current study we aimed to generate initial benchmark values for thermal desorption–gas chromatography–mass spectrometry (TD–GC–MS) analysis of breath samples containing peppermint-derived VOCs using data from three independent European research groups. Initially, headspace analysis of peppermint oil capsules was performed to determine compounds of interest. Ten healthy participants were recruited by each three groups across Europe. The standard Peppermint protocol was followed. In brief, each participant provided a baseline breath sample prior to taking a peppermint capsule, with further samples collected at 60, 90, 165, 285 and 360 min following ingestion. Sampling and analytical protocols were different for each group, in line with their usual practice. Samples were analysed by TD–GC–MS and benchmarking values determined for the time taken for detected peppermint VOCs to return to baseline values. Sixteen compounds were identified in the capsule headspace, and all were confirmed in breath following ingestion of the peppermint capsules. Additionally, 2,3-dehydro-1,8-cineole was uniquely found in the breath samples, with a washout profile that suggested it was a product of metabolism of peppermint compounds. Five compounds (α-pinene, β-pinene, eucalyptol, menthol and menthone) were quantified by all three groups. Differences were observed between the groups, particularly for the recovery of menthone and menthol. The average time taken for VOCs to return to baseline was selected as the benchmark and were 377, 423, 533, 418 and 336 min for α-pinene, β-pinene, eucalyptol, menthone and menthol respectively. We have presented an initial set of easy-to-measure benchmarking values for assessing the performance of TD–GC–MS systems for the analysis of VOCs in breath. These values will be updated when more groups provide additional data., Journal of Breath Research, 15 (2), ISSN:1752-7155, ISSN:1752-7163

Breath analysis is an expanding scientific field with great potential for creating personalized and non-invasive health screening and diagnostics techniques. However, the wide range of contradictory results in breath analysis is explained by the lack of an optimal standard procedure for selective breath sampling. Recently we developed novel instrumentation for selective breath sampling, enabling the precise collection of a pre-determined portion of exhaled air using AI (Machine Learning) algorithm. This work presents pilot study results for validation of developed technology by differentiation of alveolar and oesophagal air obtained from the healthy population (n = 31). The samples were analyzed in-situ by Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) apparatus, and obtained spectra were processed with proper multivariate classification tools. The results show a promising performance of proposed AI-based technology for breath sampling adapted to users’ age, genre, and physiological conditions.

Exhaled breath analysis for early disease detection may provide a convenient method for painless and non-invasive diagnosis. In this work, a novel, compact and easy-to-use breath analyzer platform with a modular sensing chamber and direct breath sampling unit is presented. The developed analyzer system comprises a compact, low volume, temperature-controlled sensing chamber in three modules that can host any type of resistive gas sensor arrays. Furthermore, in this study three modular breath analyzers are explicitly tested for reproducibility in a real-life breath analysis experiment with several calibration transfer (CT) techniques using transfer samples from the experiment. The experiment consists of classifying breath samples from 15 subjects before and after eating a specific meal using three instruments. We investigate the possibility to transfer calibration models across instruments using transfer samples from the experiment under study, since representative samples of human breath at some conditions are difficult to simulate in a laboratory. For example, exhaled breath from subjects suffering from a disease for which the biomarkers are mostly unknown. Results show that many transfer samples of all the classes under study (in our case meal/no meal) are needed, although some CT methods present reasonably good results with only one class., publishedVersion

Introduction Investigating acute multifactorial undifferentiated breathlessness and understanding the driving inflammatory processes can be technically challenging in both adults and children. Being able to validate noninvasive methods such as breath analysis would be a huge clinical advance. The ReCIVA® device allows breath samples to be collected directly onto sorbent tubes at the bedside for analysis of exhaled volatile organic compounds (eVOCs). We aimed to assess the feasibility of using this device in acutely breathless patients. Methods Adults hospitalised with acute breathlessness and children aged 5–16 years with acute asthma or chronic stable asthma, as well as healthy adult and child volunteers, were recruited. Breath samples were collected onto sorbent tubes using the ReCIVA® device and sent for analysis by means of two-dimensional gas chromatography-mass spectrometry (GCxGC-MS). The NASA Task Load Index (NASA-TLX) was used to assess the perceived task workload of undertaking sampling from the patient's perspective. Results Data were available for 65 adults and 61 children recruited. In total, 98.4% of adults and 75.4% of children were able to provide the full target breath sample using the ReCIVA® device. NASA-TLX measurements were available in the adult population with mean values of 3.37 for effort, 2.34 for frustration, 3.8 for mental demand, 2.8 for performance, 3.9 for physical demand and 2.8 for temporal demand. Discussion This feasibility study demonstrates it is possible and acceptable to collect breath samples from both adults and children at the bedside for breathomics analysis using the ReCIVA® device., It is feasible to collect breath samples for breath analysis at the bedside using the ReCIVA device in acutely breathless adults and children https://bit.ly/2ZTonWo

Smokers are exposed to more than 6000 toxic smoke components including volatile organic compounds (VOCs). The objective is to investigate VOCs levels in blood and exhaled breath and their relation, upon smoking three types of cigarettes of one brand with varying declared tar, nicotine and carbon monoxide (TNCO) yields according to ISO 3308. Furthermore, we aim to identify the relevance of these declared yields for human smokers exposed to VOCs. Blood and exhaled breath were sampled from twelve male volunteers directly before and 10 minutes after smoking cigarettes on 3 days (day 1 Marlboro Red (regular), day 2 Marlboro Prime (highly ventilated, low-TNCO), day 3 Marlboro Prime with blocked filter ventilation (taped)). Our results show that levels of toluene, ethylbenzene, m/p-xylene, o-xylene, and 2,5-dimethylfuran in both blood and exhaled breath increase after smoking a cigarette. Overall, no strong correlation was found between VOC levels in exhaled breath and VOC levels in blood because of variations between the individual smoking volunteers. More research is required in order to use exhaled breath sampling as a non-invasive quantitative marker for volatile toxicants from cigarette smoke exposure in risk assessment. However, we also show that the increases in concentrations in blood and exhaled breath for each smoker are within the same range for all three cigarette types smoked. The differences in declared TNCO yields, as determined with machine smoking according to ISO 3308 regime, are thus irrelevant for the assessment of human exposure of VOCs, which is important for the risk assessment of inhaling mainstream cigarette smoke. Lastly, cigarettes with lower declared TNCO levels may expose smokers to similar or even higher levels of smoke toxicants. Clinical trial registration: NCT03498053.

The influence of breath sampling on exhaled carbon monoxide (eCO) and related pulmonary gas exchange parameters is investigated in a study with 32 healthy non-smokers. Mid-infrared tunable diode laser absorption spectroscopy and well-controlled online sampling is used to precisely measure mouth- and nose-exhaled CO expirograms at exhalation flow rates (EFRs) of 250, 120 and 60 ml s−1, and for 10 s of breath-holding followed by exhalation at 120 ml s−1. A trumpet model with axial diffusion is employed to fit simulated exhalation profiles to the experimental expirograms, which provides equilibrium airway and alveolar CO concentrations and the average lung diffusing capacity in addition to end-tidal concentrations. For all breathing maneuvers, excellent agreement is found between mouth- and nose-exhaled end-tidal CO (ETCO), and the individual values for ETCO and alveolar diffusing capacity are consistent across maneuvers. The eCO parameters clearly show a dependence on EFR, where the lung diffusing capacity increases with EFR, while ETCO slightly decreases. End-tidal CO is largely independent of ambient air CO and alveolar diffusing capacity. While airway CO is slightly higher than, and correlates strongly with, ambient air CO, and there is a weak correlation with ETCO, the results point to negligible endogenous airway CO production in healthy subjects. An EFR of around 120 ml s−1 can be recommended for clinical eCO measurements. The employed method provides means to measure variations in endogenous CO, which can improve the interpretation of exhaled CO concentrations and the diagnostic value of eCO tests in clinical studies. Clinical trial registration number: 2017/306-31

Background It has been reported that canine scent tests offer the possibility to screen for cancer. Assuming that breath samples can be collected with carrier materials, we tested the practicability of different carrier materials to be presented to dogs, and validated and compared results with an eNose. Moreover, we hypothesised that cancer detection ability of dogs differs according to their working experience. Materials and Methods In a methodological approach two dog teams participated, one using experienced working dogs and the other ordinary household dogs to find discover which dogs were better qualified and the best training method. To find best carrier material for breath sampling we compared charcoal containing glass tubes with fleece masks. In a second validating part, experienced working dogs were trained with improved training strategies. For breath sampling two different, previously successfully tested fleece-based carrier materials were used: one was used with the dog team and both materials were compared with eNose. Results In the first part of the study it was shown overall that experienced working dogs performed better to family dogs and the dogs achieved a sensitivity of 45–59% and a specificity of 45–69%. Charcoal based breath sample carrier materials did not qualify for detection of VOC by dogs. In the second part of the study, the dogs achieved a specificity of 83% and a sensitivity of 56%, but with considerable differences between individual dogs. The eNose provided a specificity of 97% for both fleece based carrier materials and a sensitivity of 89% for fleece filled glass tubes and 100% for earloop masks. Measurements of breath samples collected directly in respiratory bags as reference measurements achieved a sensitivity and specificity of 100%. Conclusions Our data confirmed that diagnostic accuracy of dogs depended on the type of dog training and on the carrier materials. A comparison of breath samples analysis with an eNose achieved better results for both, sensitivity and specificity, than for dogs. The use of fleece masks or fleeces in glass tubes as a sampling material can be recommended as successful VOC carriers, encouraging their use for clinical screenings. Disclosure Information W. Biehl: None. H. Schmetzer: None. R. Koczulla: None. A. Hattesohl: None. R. Jorres: None. T. Duell: None. U. Althohn: None.

In this review, applications of near-infrared photoacoustic spectroscopy are presented as an opportunity to evaluate human respiration because the measurement of breath is fast, intact and simple to implement. Recently, analytical methods for measuring biomarkers in exhaled air have been extensively developed. With laser-based photoacoustic spectroscopy, volatile organic compounds can be identified with high sensitivity, at a high rate, and with very good selectivity. The literature review has shown the applicability of near-infrared photoacoustic spectroscopy to one of the problems of the real world, i.e., human health. In addition, the review will consider and explore different breath sampling methods for human respiration analysis.

Gas-sensing applications commonly use nanomaterials (NMs) because of their unique physicochemical properties, including a high surface-to-volume ratio, enormous number of active sites, controllable morphology, and potential for miniaturisation. NM-based gas sensors, as a noninvasive, real-time technique, are a promising candidate for monitoring human breath. This review focuses on NM-based gas sensors used for breath diagnosis. First we describe some representative biomarkers of diseases that are detectable in breath and requirements for breath sensors. Then we review electrical, optical and mass-sensitive gas sensors in terms of these performance requirements, together with describing the detection capability of these sensors for trace concentrations of biomarkers and their initial attempts to diagnose disease. Moreover, we discuss breath sensor platforms with a multivariable sensing system, wireless communication and breath sampling, essential for predictive, preventive, personalised, and participatory (“P4”) medicine. Finally, we conclude with problems and challenges associated with the selectivity, humidity and validation of breath sensors. We hope that this article will inspire the development of high-performance gas sensors based on novel NMs.

The identification of volatile compounds detected through breath sampling is generally performed using mass spectrometry (MS). The data, including extracted masses, formulae, and retention indices, coupled with searching against reference databases, are essential for the identification of candidate chemicals detected in the breath. The application of cheminformatics approaches to support this chemical identification process is an increasingly important component of MS analyses. The US EPA CompTox Chemicals Dashboard is a rich repository of chemistry- and environmental toxicology–related data for ∼875,000 chemical substances and delivers specific functionality to support MS analyses. Flexible search capabilities, the aggregation of chemical lists of interest to defined areas of research, and the ability to use metadata-based candidate ranking make the Dashboard a valuable tool in the armory of biomarker discovery studies. The application of the Dashboard to support breath research using MS is discussed and future developments are outlined.

Despite promising results obtained in the early diagnosis of several pathologies, breath analysis still remains an unused technique in clinical practice due to the lack of breath sampling standardized procedures able to guarantee a good repeatability and comparability of results. The most diffuse on an international scale breath sampling method uses polymeric bags, but, recently, devices named Mistral and ReCIVA, able to directly concentrate volatile organic compounds (VOCs) onto sorbent tubes, have been developed and launched on the market. In order to explore performances of these new automatic devices with respect to sampling in the polymeric bag and to study the differences in VOCs profile when whole or alveolar breath is collected and when pulmonary wash out with clean air is done, a tailored experimental design was developed. Three different breath sampling approaches were compared: (a) whole breath sampling by means of Tedlar bags, (b) the end-tidal breath collection using the Mistral sampler, and (c) the simultaneous collection of the whole and alveolar breath by using the ReCIVA. The obtained results showed that alveolar fraction of breath was relatively less affected by ambient air (AA) contaminants (p-values equal to 0.04 for Mistral and 0.002 for ReCIVA Low) with respect to whole breath (p-values equal to 0.97 for ReCIVA Whole). Compared to Tedlar bags, coherent results were obtained by using Mistral while lower VOCs levels were detected for samples (both breath and AA) collected by ReCIVA, likely due to uncorrected and fluctuating flow rates applied by this device. Finally, the analysis of all data also including data obtained by explorative analysis of the unique lung cancer (LC) breath sample showed that a clean air supply might determine a further confounding factor in breath analysis considering that lung wash-out is species-dependent.

Sampling of volatile organic compounds (VOCs) has shown promise for detection of a range of diseases but results have proved hard to replicate due to a lack of standardization. In this work we introduce the 'Peppermint Initiative'. The initiative seeks to disseminate a standardized experiment that allows comparison of breath sampling and data analysis methods. Further, it seeks to share a set of benchmark values for the measurement of VOCs in breath. Pilot data are presented to illustrate the standardized approach to the interpretation of results obtained from the Peppermint experiment. This pilot study was conducted to determine the washout profile of peppermint compounds in breath, identify appropriate sampling time points, and formalise the data analysis. Five and ten participants were recruited to undertake a standardized intervention by ingesting a peppermint oil capsule that engenders a predictable and controlled change in the VOC profile in exhaled breath. After collecting a pre-ingestion breath sample, five further samples are taken at 2, 4, 6, 8, and 10 h after ingestion. Samples were analysed using ion mobility spectrometry coupled to multi-capillary column and thermal desorption gas chromatography mass spectrometry. A regression analysis of the washout data was used to determine sampling times for the final peppermint protocol, and the time for the compound measurement to return to baseline levels was selected as a benchmark value. A measure of the quality of the data generated from a given technique is proposed by comparing data fidelity. This study protocol has been used for all subsequent measurements by the Peppermint Consortium (16 partners from seven countries). So far 1200 breath samples from 200 participants using a range of sampling and analytical techniques have been collected. The data from the consortium will be disseminated in subsequent technical notes focussing on results from individual platforms. The Marie Sklodowska-Curie Actions Innovative Training Network: Ion-Molecule Processes for Analytical Chemistry Technologies (IMPACT) (www.impact-h2020itn.com), which has supported BH, MM and GP as Early Stage Researchers through the European Commission's HORIZON 2020 Programme under Grant Agreement Number 674911. The EMBER consortium for support in the dissemination of the Peppermint Initiative; researchers involved in the application of the protocol to specific techniques (to be published in due course) Abigail Joyce, Amisha Manek, Bellagambi Francesca Giuseppa, Bonsignori Alessio, Ghimenti Silvia and Biagini Denise, Liesl Carr, Luke Bryant and Rebecca Cordell. MW and SJF are supported by the NIHR Manchester Biomedical Research Centre. The group from Li`ege University is supported by the FNRS through the EOS and the FRIA initiatives. Ruszkiewicz, DM (, orresponding author), Loughborough Univ, Ctr Analyt Sci, Dept Chem, Loughborough, Leics, England ; Univ Birmingham, Sch Phys & Astron, Mol Phys Grp, Birmingham, W Midlands, England. D.M.Ruszkiewicz2@lboro.ac.uk

Modern work environment is changing from classic physiological to more psychological workloads. The capability to monitor biochemical processes within the human body positions breath analysis as a promising method to non-invasively and quickly detect mental stress. The present work aims to identify psychological stress biomarkers and breath profile changes after psychological interventions (PASAT or relaxing videos). In an exploratory study, 14 male participants followed a double cross-over randomized study which included two experimental sessions (stress and neutral/relax). GSR and HR were continuously measured to indicate physiological stress levels. NASA-TLX questionnaires were fulfilled to quantify individual stress. Breath samples were selectively collected by a recently developed advanced breath sampling prototype device and afterwards analyzed with a GC-IMS apparatus. Some promising results on mental stress detection were found and are presented and discussed in this paper.

In parallel to the advances made by the human breath analysis community, significant research has also developed an understanding of breath biomarkers in marine mammals. Several different breath sampling methods have been developed, and these approaches can be used to assess animal health in both wild free-ranging animals and those under managed human care. These methods are summarized in this chapter, and differences between the sampling methods are highlighted and critiqued. A commentary on significant breath biomarkers that have been elucidated in the published literature is provided. Future research trends are also presented for this small yet important research community.

Success in breath biomarker discovery is driven by many factors, but sampling plays perhaps the most decisive role; inadequate sampling procedures can compromise breath samples, rendering them unreliable or unusable. The critical influence of sampling on data validity in breathborne biomarker applications has received widespread awareness and acceptance in the breath research community in recent years. Increasingly, efforts are being made in tailoring and standardizing sampling approaches to minimize variability and potential confounders. Aligned with these initiatives are considerations on standardized approaches for other aspects of breath research, including analytical platforms, representative patient/control cohorts, and data pre/postprocessing. This chapter explores aspects of sampling and issues that should be considered in procuring robust and reliable breath samples in both untargeted biomarker discovery and targeted biomarker validation. Further, the issue of standardization—and current lack thereof—in breath analysis is addressed, with a discussion on potential approaches to harmonize breath research pursuits.

Novel diagnostics have much promise, but they can be difficult to develop from concept to clinical utility. Herein, we review concepts germane to breath research, including metabolite selection and development vision, and offer some practical guidance. Although breath sampling is safe and can inexpensively and quickly deliver measurement results, clinical research evaluating breath analysis must adhere to the same safety and efficacy standards as other forms of clinical trials. A cohesive and well-resourced multidisciplinary team is required. Convincing results are expensive and time consuming to obtain, but essential for clinical, and ultimately, commercial success.

Breath analysis is an emerging field in gas sensor technology aiming for the next generation of hand-held and non-invasive medical diagnostic and monitoring devices. Often unrecognized, however, remains the importance of correct and standardized breath sampling, a prerequisite for meaningful breath analysis. Here, a simple and modular sampler design is presented that enables monitored breath extraction for reproducible and online gas sensor analysis. It consists of an inlet to monitor airway pressure and CO2 concentration online during exhalation and a tube to capture and buffer (20–40 s) end-tidal breath to meet prolonged exposure requirements of some gas sensors. Demonstrated on the example of acetone, a breath marker for fat burn, this sampler is suitable for continuous (refreshment ∼100 s) and reproducible online breath analysis, as validated by state-of-the-art proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS). Most interestingly, even short breath pulses down to 1 s result in reliable determination of end-tidal acetone concentrations while it is severely underestimated when sampling is not done properly. Finally, this sampler is applied to detect breath acetone with solid-state Si-doped WO3 sensors in humans. The proposed sampler can be connected to various types of gas sensors and applied flexibly for other breath markers (including isoprene, ethanol and methanol).

The data contained in this article are PubMed search strings and search string builders used to curate breath research manuscripts published from 1995–2016 and the respective number of articles found that satisfied the search requirements for selected categories. Breath sampling represents a non-invasive technique that has gained usefulness for public health, clinical, diagnostic, and environmental exposure assessment applications over the years. This data article includes search strings that were utilized to retrieve publications through the PubMed database for different breath research-related topics that were related to the analysis of exhaled breath, exhaled breath condensate (EBC), and exhaled breath aerosol (EBA) as well as the analysis of cellular headspace. Manuscripts were curated for topics including EBC, EBA, Direct MS, GC–MS, LC-MS, alcohol, and sensors. A summary of the number of papers published per year for the data retrieved using each of the search strings is also included. These data can be utilized to discern trends in the number of breath research publications in each of the different topics over time. A supplementary Appendix A containing the titles, author lists, journal names, publication dates, PMID numbers, and EntrezUID numbers for each of the journal articles curated using the finalized search strings for the seven breath research-related topics can also be found within this article. The selected manuscripts can be used to explore the impact that breath research has had on expanding the scientific knowledge in each of the investigated topics. Keywords: Exhaled breath, Exhaled breath condensate (EBC), Exhaled breath aerosol (EBA), Mass spectrometry, Sensors, Immunochemistry, Public health, Clinical diagnosis

As a futuristic diagnosis platform, breath analysis is gaining much attention because it is a noninvasive, simple, and low cost diagnostic method. Very promising clinical applications have been demonstrated for diagnostic purposes by correlation analysis between exhaled breath components and specific diseases. In addition, diverse breath molecules, which serve as biomarkers for specific diseases, are precisely identified by statistical pattern recognition studies. To further improve the accuracy of breath analysis as a diagnostic tool, breath sampling, biomarker sensing, and data analysis should be optimized. In particular, development of high performance breath sensors, which can detect biomarkers at the ppb-level in exhaled breath, is one of the most critical challenges. Due to the presence of numerous interfering gas species in exhaled breath, selective detection of specific biomarkers is also important. This Account focuses on chemiresistive type breath sensors with exceptionally high sensitivity and selectivity that were developed by combining hollow protein templated nanocatalysts with electrospun metal oxide nanostructures. Nanostructures with high surface areas are advantageous in achieving high sensitivity because the sensing signal is dominated by the surface reaction between the sensing layers and the target biomarkers. Furthermore, macroscale pores between one-dimensional (1D) nanostructures can facilitate fast gas diffusion into the sensing layers. To further enhance the selectivity, catalytic functionalization of the 1D metal oxide nanostructure is essential. However, the majority of conventional techniques for catalytic functionalization have failed to achieve a high degree of dispersion of nanoscale catalysts due to aggregation on the surface of the metal oxide, which severely deteriorates the sensing properties by lowering catalytic activity. This issue has led to extensive studies on monolithically dispersed nanoscale particles on metal oxides to maximize the catalytic performances. As a pioneering technique, a bioinspired templating route using apoferritin, that is, a hollow protein cage, has been proposed to obtain nanoscale (∼2 nm) catalyst particles with high dispersity. Nanocatalysts encapsulated by a protein shell were first used in chemiresistive type breath sensors for catalyst functionalization on 1D metal oxide structures. We discuss the robustness and versatility of the apoferrtin templating route for creating highly dispersive catalytic NPs including single components (Au, Pt, Pd, Rh, Ag, Ru, Cu, and La) and bimetallic catalysts (PtY and PtCo), as well as the core-shell structure of Au-Pd (Au-core@Pd-shell). The use of these catalysts is essential to establish high performance sensors arrays for the pattern recognition of biomarkers. In addition, novel multicomponent catalysts provide unprecedented sensitivity and selectivity. With this in mind, we discuss diverse synthetic routes for nanocatalysts using apoferritin and the formation of various catalyst-1D metal oxide composite nanostructures. Furthermore, we discuss detection capability of a simulated biomarker gas using the breath sensor arrays and principal component analysis. Finally, future prospects with the portable breath analysis platform are presented by demonstrating the potential feasibility of real-time and on-site breath analysis using chemiresistive sensors.

In lung cancer, the prognosis and treatment options depend directly on tumor size and its spread at the time of diagnosis. There is therefore a constant search for methods that will allow early detection of cancerous lung nodules. With advancing imaging technology and implantation of screening routines in high-risk populations by low-dose computerized tomography, a significant increase in the number of diagnosed small peripheral lesions can be expected. While early detection of small cancerous lesions carries the benefit of wider treatment options and better prognosis, the process of obtaining a biopsy to confirm a cancerous tissue is not free of complications and bears inconveniences and stress to the patient. This review discusses the potential use of exhaled breath analysis as a simple, noninvasive tool for early detection of lung cancer and characterization of suspicious lung nodules.

Mercury (Hg) is a naturally occurring element that has metallic, inorganic and organic forms, each with their own implications for human health. Exposure to mercury primarily occurs by inhalation of metallic mercury vapors and by dietary intake of organic mercury. Early health effects are often not well detected. Therefore, determination of the internal dose is a valuable approach in primary prevention. With this review, we aim to give an overview of the different human biological monitoring (HBM) approaches for short- and long-term exposure to different chemical forms of mercury. We performed a literature search in PubMed using Medical Subject Headings (MeSH) terms as well as free text words. From 417 reviews found, we selected 8 reviews. In addition, online information from national and international health authorities was used. The format of the biological application datasheets from the BIOMONECS project was used to provide an overview of the different biological media for HBM of mercury and methyl mercury. Recent exposure to metallic mercury can be assessed by blood sampling within 24 h after exposure. If children are involved, breath sampling can be considered as a less invasive alternative. Urinary mercury levels mainly reflect long-term inhalation exposure to elemental mercury vapors and divalent mercury. Mercury in blood and hair reflects mid- and long-term exposure to methyl mercury, whereas analysis of a hair segment close to the scalp indicates recent exposure. A flow chart was developed to support the selection of the most suitable HBM approach. For each of the different biological matrices, we provided an overview of advantages and limitations. Depending on the source and duration of exposure, blood, exhaled air, urine or hair can be used for mercury exposure assessment.