Metabolomics Diagnosis of COVID-19 from Exhaled Breath Condensate.
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ABSTRACT:
SUBMITTER: Barberis E
PROVIDER: S-EPMC8708149 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Exhaled breath condensate (EBC) analysis is a developing field with tremendous promise to advance personalized, non-invasive health diagnostics as new analytical instrumentation platforms and detection methods are developed. Multiple commercially-available and researcher-built experimental samplers are reported in the literature. However, there is very limited information available to determine an effective breath sampling approach, especially regarding the dependence of breath sample metabolomic content on the collection device design and sampling methodology. This lack of an optimal standard procedure results in a range of reported results that are sometimes contradictory. Here, we present a design of a portable human EBC sampler optimized for collection and preservation of the rich metabolomic content of breath. The performance of the engineered device is compared to two commercially available breath collection devices: the RTube™ and TurboDECCS. A number of design and performance parameters are considered, including: condenser temperature stability during sampling, collection efficiency, condenser material choice, and saliva contamination in the collected breath samples. The significance of the biological content of breath samples, collected with each device, is evaluated with a set of mass spectrometry methods and was the primary factor for evaluating device performance. The design includes an adjustable mass-size threshold for aerodynamic filtering of saliva droplets from the breath flow. Engineering an inexpensive device that allows efficient collection of metalomic-rich breath samples is intended to aid further advancement in the field of breath analysis for non-invasive health diagnostic. EBC sampling from human volunteers was performed under UC Davis IRB protocol 63701-3 (09/30/2014-07/07/2017).
| S-EPMC5447364 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) is characterized by different phenotypes and clinical presentations. Therefore, a single strategy of pulmonary rehabilitation (PR) does not always yield the expected clinical outcomes as some individuals respond excellently, others discreetly, or do not respond at all. Fifty consecutive COPD patients were enrolled. Of them, 35 starting a 5-week PR program were sampled at admission (T0), after 2 (T2W) and 5 (T5W) weeks, while 15 controls not yet on PR were tested at T0 and T5W. Nuclear magnetic resonance (NMR) profiling of exhaled breath condensate (EBC) and multivariate statistical analysis were applied to investigate the relationship between biomarkers and clinical parameters. The model including the three classes correctly located T2W between T0 and T5W, but 38.71% of samples partially overlapped with T0 and 32.26% with T5W, suggesting that for some patients PR is already beneficial at T2W (32.26% overlapping with T5W), while for others (38.71% overlapping with T0) more time is required. Rehabilitated patients presented several altered biomarkers. In particular, methanol from T0 to T5W decreased in parallel with dyspnea and fatigue, while the walk distance increased. Methanol could be ascribed to lung inflammation. We demonstrated that the metabolic COPD phenotype clearly evolves during PR, with a strict relationship between clinical and molecular parameters. Methanol, correlating with clinical parameters, represents a useful biomarker for monitoring personalized outcomes and establishing more targeted protocols.
| S-EPMC8834302 | biostudies-literature
Project description:ObjectiveThis study aims to ascertain the unique metabolic profile of exhaled breath condensate (EBC) samples in pulmonary aspergillosis (PA) patients, and explore their usefulness for the diagnosis of PA.MethodsA total of 133 patients were included in the study, including 66 PA patients (invasive pulmonary aspergillosis, n=3; chronic pulmonary aspergillosis, n=60; allergic bronchopulmonary aspergillosis, n=3) and controls (n=67). Ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry(UHPLC-HRMS) was used to analyze EBC samples. Metabolic profiling of EBC samples that were collected from 22 CPA patients at various times during treatment (before treatment, <1 month, 1-2 months, 2-3 months, 3-6 months, and ≥6 months after treatment initiation) were performed using UHPLC-HRMS. Potential biomarkers were evaluated using cluster analysis, Venn diagram and receiver operating characteristic analysis (ROC).ResultsA total of 47 metabolites of potential interest were detected in the EBC samples. Further investigation showed that Asperpyrone C, Kotanin, Terphenyllin, Terrelumamide B, and Cyclotryprostatin D could be used as a diagnostic biomarker for PA. The classification between metabolic profiling of EBC samples from PA patients and controls was good with a sensitivity of 100%, specificity 89.6% for patients with PA, respectively. Venn diagram analysis of these biomarker candidates displayed three main types of compounds, which could be used for the further discrimination of aspergilloma and chronic cavitary PA. In addition, antifungal treatment had a limited influence on the value of the EBC results.ConclusionsThis metabolomic approach using UHPLC-HRMS could be used as a noninvasive method for the diagnosis of PA.
| S-EPMC9492867 | biostudies-literature
Project description:Thiocyanate is a heme peroxidase substrate that scavenges oxidants produced during inflammation and regulates host defense. In cystic fibrosis (CF) patients, increased airway thiocyanate levels are associated with improved lung function. Research on airway thiocyanate is limited, however, because convenient non-invasive airway sampling methods, such as exhaled breath condensate (EBC), yield low concentrations that are difficult to detect with available assays. In the present study, we developed a method for the determination of thiocyanate in dilute samples using isotope dilution headspace gas chromatography-coupled high-resolution, accurate-mass mass spectrometry (GC-HRMS). The method reliably quantified as little as 4 pmol thiocyanate in EBC and could detect even lower amounts. We successfully measured thiocyanate in EBC from seven healthy donors, with a mean ± SD of 27 ± 16 nM and a median inter-assay coefficient of variation of 10.4% over six months. The method was applied to other biological fluids (plasma from the same visit as EBC donation; bronchoalveolar lavage fluid [BALF] from infants with CF; and healthy adult mouse BALF), giving reliable quantification of samples ranging from 10 nM to 100 µM. Thiocyanate concentrations in fluids besides EBC were (from lowest to highest): 0.73 ± 0.39 µM in BALF of healthy adult mice (n = 6); 1.4 ± 1.4 µM in BALF from infants with CF (n = 24); 46 ± 22 µM in the plasma of adult volunteers (n = 7). These results demonstrate the utility of this new method for clinical determination of thiocyanate in EBC and other biological fluids.
| S-EPMC6166650 | biostudies-literature
Project description:BackgroundEarly diagnosis of coronavirus disease 2019 (COVID-19) is of the utmost importance but remains challenging. The objective of the current study was to characterize exhaled breath from mechanically ventilated adults with COVID-19.MethodsIn this prospective observational study, we used real-time, online, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of expired air from adults undergoing invasive mechanical ventilation in the intensive care unit due to severe COVID-19 or non-COVID-19 acute respiratory distress syndrome (ARDS).FindingsBetween March 25th and June 25th, 2020, we included 40 patients with ARDS, of whom 28 had proven COVID-19. In a multivariate analysis, we identified a characteristic breathprint for COVID-19. We could differentiate between COVID-19 and non-COVID-19 ARDS with accuracy of 93% (sensitivity: 90%, specificity: 94%, area under the receiver operating characteristic curve: 0·94-0·98, after cross-validation). The four most prominent volatile compounds in COVID-19 patients were methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal.InterpretationThe real-time, non-invasive detection of methylpent-2-enal, 2,4-octadiene 1-chloroheptane, and nonanal in exhaled breath may identify ARDS patients with COVID-19.FundingThe study was funded by Agence Nationale de la Recherche (SoftwAiR, ANR-18-CE45-0017 and RHU4 RECORDS, Programme d'Investissements d'Avenir, ANR-18-RHUS-0004), Région Île de France (SESAME 2016), and Fondation Foch.
| S-EPMC7714658 | biostudies-literature
Project description:The lung microbiota is commonly sampled using relatively invasive bronchoscopic procedures. Exhaled breath condensate (EBC) collection potentially offers a less invasive alternative for lung microbiota sampling. We compared lung microbiota samples retrieved by protected specimen brushings (PSB) and exhaled breath condensate collection. We also sought to assess whether aerosolized antibiotic treatment would influence the lung microbiota and whether this change could be detected in EBC. EBC was collected from 6 conscious sheep and then from the same anesthetized sheep during mechanical ventilation. Following the latter EBC collection, PSB samples were collected from separate sites within each sheep lung. On the subsequent day, each sheep was then treated with nebulized colistimethate sodium. Two days after nebulization, EBC and PSB samples were again collected. Bacterial DNA was quantified using 16S rRNA gene quantitative PCR. The V2-V3 region of the 16S rRNA gene was amplified by PCR and sequenced using Illumina MiSeq. Quality control and operational taxonomic unit (OTU) clustering were performed with mothur. The EBC samples contained significantly less bacterial DNA than the PSB samples. The EBC samples from anesthetized animals clustered separately by their bacterial community compositions in comparison to the PSB samples, and 37 bacterial OTUs were identified as differentially abundant between the two sample types. Despite only low concentrations of colistin being detected in bronchoalveolar lavage fluid, PSB samples were found to differ by their bacterial compositions before and after colistimethate sodium treatment. Our findings indicate that microbiota in EBC samples and PSB samples are not equivalent.IMPORTANCE Sampling of the lung microbiota usually necessitates performing bronchoscopic procedures that involve a hospital visit for human participants and the use of trained staff. The inconvenience and perceived discomfort of participating in this kind of research may deter healthy volunteers and may not be a safe option for patients with advanced lung disease. This study set out to evaluate a less invasive method for collecting lung microbiota samples by comparing samples taken via protected specimen brushings (PSB) to those taken via exhaled breath condensate (EBC) collection. We found that there was less bacterial DNA in EBC samples compared with that in PSB samples and that there were differences between the bacterial communities in the two sample types. We conclude that while EBC and PSB samples do not produce equivalent microbiota samples, the study of the EBC microbiota may still be of interest.
| S-EPMC5452816 | biostudies-literature
Project description:Inflammation is a comprehensive set of physiological processes that an organism undertakes in response to a wide variety of foreign stimuli, such as viruses, bacteria, and inorganic particles. A key role is played by cytokines, protein-based chemical mediators produced by a broad range of cells, including the immune cells recruited in the inflammation site. The aim of this systematic review is to compare baseline values of pro/anti-inflammatory biomarkers measured in Exhaled Breath Condensate (EBC) in healthy, non-smoking adults to provide a summary of the concentrations reported in the literature. We focused on: interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-α), and C reactive protein (CRP). Eligible articles were identified in PubMed, Embase, and Cochrane CENTRAL. Due to the wide differences in methodologies employed in the included articles concerning EBC sampling, storage, and analyses, research protocols were assessed specifically to test their adherence to the ATS/ERS Task Force guidelines on EBC. The development of reference intervals for these biomarkers can result in their introduction and use in both research and clinical settings, not only for monitoring purposes but also, in the perspective of future longitudinal studies, as predictive parameters for the onset and development of chronic diseases with inflammatory aetiology.
| S-EPMC9456215 | biostudies-literature
Project description:The present study explored whether the proteomic analysis of exhaled breath condensate (EBC) may provide potential biomarkers for their use in non-invasive screening strategies for the early detection of lung cancer (LC). EBC was collected from 192 individuals (49 control volunteers, 49 risk factor-smoking volunteers, 46 chronic obstructive pulmonary disease patients and 48 LC patients). Using LC-MS/MS a total of 348 different proteins with a different pattern among the four groups were identified in EBC samples. Despite the great variability observed among individuals, significantly more proteins were identified in the EBC from LC patients compared to other groups. Furthermore, the average number of proteins identified per sample was significantly higher in LC patients and Receiver Operating Characteristic curve analysis showed an area under the curve of 0.8, indicating diagnostic value. Proteins frequently detected in EBC, such as dermcidin and hornerin, along with others much less frequently detected, such as hemoglobin and histone isoforms, were identified. Cytokeratins (KRTs) were the most abundant proteins in EBC samples and levels of KRT6A, KRT6B and KRT6C isoforms were significantly higher in samples from LC patients. Moreover, the amount of most KRTs in EBC samples from LC patients showed a significant positive correlation with tumor size. Finally, we used a random forest algorithm to generate a robust model using EBC protein data for the diagnosis of patients with LC. Thus, this study demonstrates that the proteomic analysis of EBC samples is an appropriated approach to develop biomarkers for the diagnosis of lung cancer.
2019-08-16 | PXD006436 | Pride
Project description:Current diagnostic markers for pulmonary embolism (PE) are unspecific. We investigated the proteome of the exhaled breath condensate (EBC) in a porcine model of acute PE in order to identify putative diagnostic markers for PE. EBC was collected at baseline and after the induction of autologous intermediate-risk PE in 14 pigs, plus four negative control pigs. The protein profiles of the EBC were analyzed using label-free quantitative nano liquid chromatography-tandem mass spectrometry. A total of 897 proteins were identified in the EBCs from the pigs. Alterations were found in the levels of 145 different proteins after PE compared with the baseline and negative controls: albumin was among the most upregulated proteins, with 14-fold higher levels 2.5 h after PE (p-value: 0.02). The levels of 49 other proteins were between 1.3- and 17.1-fold higher after PE. The levels of 95 proteins were lower after PE. Neutrophil gelatinase-associated lipocalin (fold change 0.3, p-value < 0.01) was among the most reduced proteins 2.5 h after PE. A prediction model based on penalized regression identified five proteins including albumin and neutrophil gelatinase-associated lipocalin. The model was capable of discriminating baseline samples from EBC samples collected 2.5 h after PE correctly in 22 out of 27 samples. In conclusion, the EBC from pigs with acute PE contained several putative diagnostic markers of PE.
| S-EPMC8584843 | biostudies-literature
Project description:Exhaled breath aerosols contain valuable metabolomic content due to gas exchange with blood at the alveolar capillary interface in the lung. Passive and selective filtering of these aerosols and droplets may reduce the amount of saliva contaminants and serve as an aid to enhance targeted metabolomic content when sampled in exhaled breath condensate (EBC). It is currently unknown if breath aerosol size distribution affects the types or abundances of metabolites sampled through EBC. This pilot study uses a previously described hand-held human breath sampler device with varying notch filter geometries to redirect the trajectory of breath aerosols based on size. Ten notch filter lengths were simulated with the device to calculate the effect of filter length on the breath aerosol size distribution and the proportion of aerosols which make their way through to an EBC collection tube. From three notch filter lengths, we investigate metabolite content of various aerosol fractions. We analyzed the non-volatile fraction of breath condensate with high performance liquid chromatography-mass spectrometry for broad metabolite coverage. We hypothesize that: (1) increasing the length of the notch filter in this device will prevent larger aerosols from reaching the collection tube thus altering the breath aerosol size distribution sampled in EBC; and (2) there is not a systematic large-scale difference in EBC metabolomic content that correlates with breath aerosol size. From simulation results, particles typically larger than 10 µm were filtered out. This indicates that a longer notch filter in this device prevents larger particles from reaching the collection tube thus altering the aerosol particle size distribution. Most compounds were commonly present in all three filter lengths tested, and we did not see strong statistical evidence of systematic metabolite differences between breath aerosol size distributions.
| S-EPMC7880424 | biostudies-literature