Journal of breath research最新文献

This paper describes the AEOLUS pilot study which combines breath analysis with cardiopulmonary exercise testing (CPET) and an echocardiographic examination for monitoring heart failure (HF) patients. Ten consecutive patients with a prior clinical diagnosis of HF with reduced left ventricular ejection fraction were prospectively enrolled together with 15 control patients with cardiovascular risk factors, including hypertension, type II diabetes or chronic ischemic heart disease. Breath samples were collected at rest and during CPET coupled with exercise stress echocardiography (CPET-ESE) protocol by means of needle trap micro-extraction and were analyzed through gas-chromatography coupled with mass spectrometry. The protocol also involved using of a selected ion flow tube mass spectrometer for a breath-by-breath isoprene and acetone analysis during exercise. At rest, HF patients showed increased breath levels of acetone and pentane, which are related to altered oxidation of fatty acids and oxidative stress, respectively. A significant positive correlation was observed between acetone and the gold standard biomarker NT-proBNP in plasma (r= 0.646,p< 0.001), both measured at rest. During exercise, some exhaled volatiles (e.g., isoprene) mirrored ventilatory and/or hemodynamic adaptation, whereas others (e.g., sulfide compounds and 3-hydroxy-2-butanone) depended on their origin. At peak effort, acetone levels in HF patients differed significantly from those of the control group, suggesting an altered myocardial and systemic metabolic adaptation to exercise for HF patients. These preliminary data suggest that concomitant acquisition of CPET-ESE and breath analysis is feasible and might provide additional clinical information on the metabolic maladaptation of HF patients to exercise. Such information may refine the identification of patients at higher risk of disease worsening.

Infection of airway epithelial cells with severe acute respiratory coronavirus 2 (SARS-CoV-2) can lead to severe respiratory tract damage and lung injury with hypoxia. It is challenging to sample the lower airways non-invasively and the capability to identify a highly representative specimen that can be collected in a non-invasive way would provide opportunities to investigate metabolomic consequences of COVID-19 disease. In the present study, we performed a targeted metabolomic approach using liquid chromatography coupled with high resolution chromatography (LC-MS) on exhaled breath condensate (EBC) collected from hospitalized COVID-19 patients (COVID+) and negative controls, both non-hospitalized and hospitalized for other reasons (COVID-). We were able to noninvasively identify and quantify inflammatory oxylipin shifts and dysregulation that may ultimately be used to monitor COVID-19 disease progression or severity and response to therapy. We also expected EBC-based biochemical oxylipin changes associated with COVID-19 host response to infection. The results indicated ten targeted oxylipins showing significative differences between SAR-CoV-2 infected EBC samples and negative control subjects. These compounds were prostaglandins A2 and D2, LXA4, 5-HETE, 12-HETE, 15-HETE, 5-HEPE, 9-HODE, 13-oxoODE and 19(20)-EpDPA, which are associated with specific pathways (i.e. P450, COX, 15-LOX) related to inflammatory and oxidative stress processes. Moreover, all these compounds were up-regulated by COVID+, meaning their concentrations were higher in subjects with SAR-CoV-2 infection. Given that many COVID-19 symptoms are inflammatory in nature, this is interesting insight into the pathophysiology of the disease. Breath monitoring of these and other EBC metabolites presents an interesting opportunity to monitor key indicators of disease progression and severity.

In this perspective, we review the evidence for the efficacy of face masks to reduce the transmission of respiratory viruses, specifically severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consider the value of mandating universal mask wearing against the widespread negative impacts that have been associated with such measures. Before the SARS-CoV-2 pandemic, it was considered that there was little to no benefit in healthy people wearing masks as prophylaxis against becoming infected or as unwitting vectors of viral transmission. This accepted policy was hastily reversed early on in the pandemic, when districts and countries throughout the world imposed stringent masking mandates. Now, more than three years since the start of the pandemic, the amassed studies that have investigated the use of masks to reduce transmission of SARS-CoV-2 (or other pathogens) have led to conclusions that are largely inconsistent and contradictory. There is no statistically significant or unambiguous scientific evidence to justify mandatory masking for general, healthy populations with the intention of lessening the viral spread. Even if mask wearing could potentially reduce the transmission of SARS-CoV-2 in individual cases, this needs to be balanced against the physical, psychological and social harms associated with forced mask wearing, not to mention the negative impact of innumerable disposed masks entering our fragile environment. Given the lack of unequivocal scientific proof that masks have any effect on reducing transmission, together with the evident harms to people and the environment through the use of masks, it is our opinion that the mandatory use of face masks in the general population is unjustifiable and must be abandoned in future pandemic countermeasures policies.

Methane (CH₄) which can be detected in human breath has long been exclusively associated with anaerobic microbial activity (methanogenesis) in the gastrointestinal tract. However, recent studies challenge this understanding by revealing that CH₄might also be produced endogenously in cells through oxidative-reductive stress reactions. Consequently, variations in breath CH₄levels compared to an individual's baseline level might indicate enhanced oxidative stress levels, and, therefore, monitoring breath CH₄levels might offer great potential for 'in vivo' diagnostics such as disease diagnosis, monitoring the efficacy of treatments, or during the application of personalized medicine. To evaluate the effects from immune responses triggered by infections, inflammations, and induced perturbation by vaccination on CH₄dynamics in breath, two subjects were monitored over a period of almost 2 years. Breath CH₄levels were measured by gas chromatography equipped with a flame-ionization detector. Both subjects exhibited significant deviations (positive and negative, respectively) from their normal CH₄breath levels during periods of potential enhanced immune activity. Deviations from the 'healthy state' were indicated by the exceeding of individual CH₄ranges. Moreover, for the first time we could clearly prove CH₄degradation induced through vaccination by measuring stable carbon isotopes of CH₄using gas chromatograph-combustion-isotope ratio mass spectrometry. Hence, breath CH₄concentration and isotopic analyses may be used as a biomarker to evaluate specific immune responses and individual immune states.

In the modern world, many people are changing old dietary and lifestyle habits to improve the quality of their living-to treat or just prevent possible diseases. The main goal of this pilot study was to assess the food and lifestyle impact on exhaled breath volatile organic compounds (VOCs) in various population groups. It was done by employing a recently validated portable membrane-inlet mass spectrometer-MIMS. Thus, the obtained results would also represent the additional confirmation for the employment of the new instrument in the breath analysis. The pilot study involved 151 participants across Europe, including people with overweight, obesity, type 2 diabetes mellitus, cardiovascular disease, people with poor-quality diet and professional athletes. Exhaled breath acetone, ethanol, isoprene, and n-pentane levels were determined in samples before the meal, and 120 min after the meal. Obtained basal ppb_vvalues were mainly in accordance with previously reported, which confirms that MIMS instrument can be used in the breath analysis. Combining the quantified levels along with the information about the participants' lifestyle habits collected via questionnaire, an assessment of the food and lifestyle impact was obtained. Notable alteration in examined VOC levels upon meal consumption was detected in more than 70% of all participants, with exception for isoprene, which was affected in about half of participants. Lifestyle parameters impact was examined using statistical analysis of variance (ANOVA) on ranks test. Statistically significant differences in basal breath VOC levels were observed among all examined population groups. Also, n-pentane and ethanol levels significantly differed in people of different ages, as well as acetone levels in people with different physical activity habits. These findings are promising for further, more focused research using MIMS technique in breath analysis.

The Peppermint Experiment is a breath analysis benchmarking initiative that seeks to address the lack of inter-comparability of outcomes across independent breath biomarker studies. In this experiment, the washout profiles of volatile terpene constituents of encapsulated peppermint oil (mainlyα-pinene,β-pinene, limonene and 1,8-cineole) in exhaled breath are characterized through a series of measurements at defined sampling intervals up to 6 h after ingestion of the capsule. In the present work, the Peppermint Experiment was carried out on a cohort of volunteers (n= 11) that provided breath samples in three sittings on different days (i.e. triplicates per volunteer) for concurrent analysis by three different analytical platforms. These platforms were proton transfer reaction-time-of-flight-mass spectrometry (PTR-TOFMS) interfaced with a buffered end-tidal (BET) breath sampler, gas chromatography-ion mobility spectrometry (GC-IMS) in conjunction with a compatible handheld direct breath sampler, and thermal desorption comprehensive two-dimensional gas chromatography-time-of-flight-mass spectrometry (TD-GC×GC-TOFMS) with a Respiration Collection forin-vitroAnalysis (ReCIVA) system for trapping breath volatiles onto adsorbent tubes. Regression analysis yielded mean washout times across the cohort of 448 min (PTR-TOFMS and GC-IMS) and 372 min (TD-GC×GC-TOFMS), which are in good alignment with published benchmark values. Large variations in washout profiles were observed at the individuals level, both between (inter-individual) and within (intra-individual) participants, indicating high variability in the degree of absorption, distribution, metabolism and excretion of volatile terpenes in the body within individuals and across the cohort. The comparably low inter-instrument variability indicates that differences in benchmark values from independent studies reported in the literature are driven by biological variability rather than different performances between sampling methods or analytical platforms.

Owing to its connection to cancer metabolism, lactate is a compound that has been a focus of interest in field of cancer biochemistry for more than a century. Exhaled breath volatile organic compounds (VOCs) and condensate analyses can identify and monitor volatile and non-VOCs, respectively, present in exhaled breath to gain information about the health state of an individual. This work aims to take into account the possible use of breath lactate measurements in tumor diagnosis and treatment control, to discuss technical barriers to measurement, and to evaluate directions for the future improvement of this technique. The use of exhaled breath condensate (EBC) lactic acid levels in disorders other than cancer is also discussed in brief. Whilst the use of EBC for the detection of lactate in exhaled breath is a promising tool that could be used to monitor and screen for cancer, the reliability and sensitivity of detection are uncertain, and hence its value in clinical practice is still limited. Currently, lactate present in plasma and EBC can only be used as a biomarker for advanced cancer, and therefore it presently has limited differential diagnostic importance and is rather of prognostic value.

Understanding particle deposition in the human lung is crucial for the assessment of environmental pollutants and the design of new drug delivery systems. Traditionally, research has been carried out by experimental analysis, but this generally requires expensive equipment and exposure of volunteers to radiation, resulting in limited data. To overcome these drawbacks, there is an emphasis on the development of numerical models capable of accurate predictive analysis. The most advanced of these computer simulations are based on three-dimensional computational fluid dynamics. Solving the flow equations in a complete, fully resolved lung airway model is currently not feasible due to the computational resources required. In the present work, a simplified lung model is presented and validated for accurate prediction of particle deposition. Simulations are performed for an 8-path approximation to a full lung airway model. A novel boundary condition method is used to ensure accurate results in truncated flow branches. Simulations are performed at a steady inhalation flow rate of 18 l min^-1, corresponding to a low activity breathing rate, while the effects of particle size and density are investigated. Comparison of the simulation results with available experimental data shows that reasonably accurate results can be obtained at a small fraction of the cost of a full airway model. The simulations clearly evaluate the effect of both particle size and particle density. Most importantly, the results show an improvement over a previously documented single-path model, both in terms of accuracy and the ability to obtain regional deposition rates. The present model represents an improvement over previously used simplified models, including single-path models. The multi-path reduced airway approach described can be used by researchers for general and patient-specific analyses of particle deposition and for the design of effective drug delivery systems.

The use of volatile biomarkers in exhaled breath as predictors to individual drug response would advance the field of personalised medicine by providing direct information on enzyme activity. This would result in enormous benefits, both for patients and for the healthcare sector. Non-invasive breath tests would also gain a high acceptance by patients. Towards this goal, differences in metabolism resulting from extensive polymorphisms in a major group of drug-metabolizing enzymes, the cytochrome P450 (CYP) family, need to be determined and quantified. CYP2C9 is responsible for metabolising many crucial drugs (e.g., diclofenac) and food ingredients (e.g., limonene). In this paper, we provide a proof-of-concept study that illustrates thein vitrobioconversion of diclofenac in recombinant HEK293T cells overexpressing CYP2C9 to 4'-hydroxydiclofenac. Thisin vitroapproach is a necessary and important first step in the development of breath tests to determine and monitor metabolic processes in the human body. By focusing on the metabolic conversion of diclofenac, we have been able to establish a workflow using a cell-based system for CYP2C9 activity. Furthermore, we illustrate how the bioconversion of diclofenac is limited in the presence of limonene, which is another CYP2C9 metabolising substrate. We show that increasing limonene levels continuously reduce the production of 4'-hydroxydiclofenac. Michaelis-Menten kinetics were performed for the diclofenac 4'-hydroxylation with and without limonene, giving a kinetic constant of the reaction,K_M, of 103µM and 94.1µM, respectively, and a maximum reaction rate,V_max, of 46.8 pmol min^-110⁶cells^-1and 56.0 pmol min^-110⁶cells^-1with and without the inhibitor, respectively, suggesting a non-competitive or mixed inhibition type. The half-maximal inhibitory concentration value (IC₅₀) for the inhibition of the formation of 4'-hydroxydiclofenace by limonene is determined to be 1413µM.