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Changes in lung epithelial cell volatile metabolite profile induced by pro-fibrotic stimulation with TGF-β1. TGF-β1促纤维化刺激对肺上皮细胞挥发性代谢物谱的影响
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-09-07 DOI: 10.1088/1752-7163/acf391
Conal Hayton, Waqar Ahmed, Peter Cunningham, Karen Piper-Hanley, Laurence Pearmain, Nazia Chaudhuri, Colm Leonard, John F Blaikley, Stephen J Fowler

Volatile organic compounds (VOCs) have shown promise as potential biomarkers in idiopathic pulmonary fibrosis. Measuring VOCs in the headspace ofin vitromodels of lung fibrosis may offer a method of determining the origin of those detected in exhaled breath. The aim of this study was to determine the VOCs associated with two lung cell lines (A549 and MRC-5 cells) and changes associated with stimulation of cells with the pro-fibrotic cytokine, transforming growth factor (TGF)-β1. A dynamic headspace sampling method was used to sample the headspace of A549 cells and MRC-5 cells. These were compared to media control samples and to each other to identify VOCs which discriminated between cell lines. Cells were then stimulated with the TGF-β1 and samples were compared between stimulated and unstimulated cells. Samples were analysed using thermal desorption-gas chromatography-mass spectrometry and supervised analysis was performed using sparse partial least squares-discriminant analysis (sPLS-DA). Supervised analysis revealed differential VOC profiles unique to each of the cell lines and from the media control samples. Significant changes in VOC profiles were induced by stimulation of cell lines with TGF-β1. In particular, several terpenoids (isopinocarveol, sativene and 3-carene) were increased in stimulated cells compared to unstimulated cells. VOC profiles differ between lung cell lines and alter in response to pro-fibrotic stimulation. Increased abundance of terpenoids in the headspace of stimulated cells may reflect TGF-β1 cell signalling activity and metabolic reprogramming. This may offer a potential biomarker target in exhaled breath in IPF.

挥发性有机化合物(VOCs)作为特发性肺纤维化的潜在生物标志物已显示出前景。在肺纤维化的体外模型中测量挥发性有机化合物的顶空可能提供一种确定呼出气体中检测到的挥发性有机化合物来源的方法。本研究的目的是确定两种肺细胞系(A549和MRC-5细胞)的VOCs相关以及促纤维化细胞因子转化生长因子(TGF)-β1刺激细胞的相关变化。采用动态顶空取样法对A549细胞和MRC-5细胞顶空取样。将这些样品与培养基对照样品进行比较,并相互比较,以确定区分细胞系的挥发性有机化合物。然后用TGF-β1刺激细胞,比较刺激细胞和未刺激细胞的样品。样品采用热解吸-气相色谱-质谱分析,监督分析采用稀疏偏最小二乘判别分析(sPLS-DA)。监督分析揭示了不同细胞系和培养基对照样品中独特的VOC特征。TGF-β1刺激细胞株后,VOC谱发生显著变化。特别是,与未受刺激的细胞相比,受刺激的细胞中几种萜类化合物(异皂荚醇、皂荚烯和3-蒈烯)增加。挥发性有机化合物谱在肺细胞系之间不同,并在促纤维化刺激下改变。受刺激细胞顶空中萜类化合物丰度的增加可能反映了TGF-β1细胞信号转导活性和代谢重编程。这可能为IPF呼出气体提供一个潜在的生物标志物靶点。
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引用次数: 0
Diagnostic accuracy of eNose 'breathprints' for therapeutic drug monitoring of Tacrolimus trough levels in lung transplantation. eNose“呼吸指纹”在肺移植中监测他克莫司谷水平的诊断准确性。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-09-05 DOI: 10.1088/1752-7163/acf066
Nynke Wijbenga, Marjolein M Muller, Rogier A S Hoek, Bas J Mathot, Leonard Seghers, Joachim G J V Aerts, Brenda C M de Winter, Daniel Bos, Olivier C Manintveld, Merel E Hellemons

In order to prevent long-term immunity-related complications after lung transplantation, close monitoring of immunosuppressant levels using therapeutic drug monitoring (TDM) is paramount. Novel electronic nose (eNose) technology may be a non-invasive alternative to the current invasive procedures for TDM. We investigated the diagnostic and categorization capacity of eNose breathprints for Tacrolimus trough blood plasma levels (TACtrough) in lung transplant recipients (LTRs). We performed eNose measurements in stable LTR attending the outpatient clinic. We evaluated (1) the correlation between eNose measurements and TACtrough, (2) the diagnostic capacity of eNose technology for TACtrough, and (3) the accuracy of eNose technology for categorization of TACtroughinto three clinically relevant categories (low: <7µg ml-1, medium: 7-10µg ml-1, and high: >10µg ml-1). A total of 186 measurements from 86 LTR were included. There was a weak but statistically significant correlation (r= 0.21,p= 0.004) between the eNose measurements and TACtrough. The root mean squared error of prediction for the diagnostic capacity was 3.186 in the training and 3.131 in the validation set. The accuracy of categorization ranged between 45%-63% for the training set and 52%-69% in the validation set. There is a weak correlation between eNose breathprints and TACtroughin LTR. However, the diagnostic as well as categorization capacity for TACtroughusing eNose breathprints is too inaccurate to be applicable in TDM.

为了预防肺移植术后长期的免疫相关并发症,使用治疗性药物监测(TDM)密切监测免疫抑制剂水平至关重要。新型电子鼻(eNose)技术可能是目前创伤性TDM手术的非侵入性替代方案。我们研究了肺移植受者(LTRs)呼气指纹通过血浆水平(TACtrough)对他克莫司的诊断和分类能力。我们对在门诊就诊的稳定LTR患者进行了eNose测量。我们评估了(1)eNose测量值与tac槽之间的相关性,(2)eNose技术对tac槽的诊断能力,以及(3)eNose技术将tac槽分为三个临床相关类别的准确性(低:µg ml-1,中:7-10µg ml-1,高:>10µg ml-1)。共纳入86个LTR的186个测量值。eNose测量值与tacthrough之间存在微弱但有统计学意义的相关性(r= 0.21,p= 0.004)。训练集预测诊断能力的均方根误差为3.186,验证集预测诊断能力的均方根误差为3.131。训练集的分类准确率为45%-63%,验证集的分类准确率为52%-69%。eNose呼气指纹与TACtroughin LTR之间的相关性较弱,然而,TACtroughin呼气指纹的诊断和分类能力太不准确,无法应用于TDM。
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引用次数: 0
Alveolar gradients in breath analysis. A pilot study with comparison of room air and inhaled air by simultaneous measurements using ion mobility spectrometry. 呼吸分析中的肺泡梯度。通过离子迁移率光谱法同时测量室内空气和吸入空气的比较初步研究。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-09-04 DOI: 10.1088/1752-7163/acf338
M Westhoff, M Keßler, J I Baumbach

Analyzing exhaled breath samples, especially using a highly sensitive method such as MCC/IMS (multi-capillary column/ion mobility spectrometry), may also detect analytes that are derived from exogenous production. In this regard, there is a discussion about the optimal interpretation of exhaled breath, either by considering volatile organic compounds (VOCs) only in exhaled breath or by additionally considering the composition of room air and calculating the alveolar gradients. However, there are no data on whether the composition and concentration of VOCs in room air are identical to those in truly inhaled air directly before analyzing the exhaled breath. The current study aimed to determine whether the VOCs in room air, which are usually used for the calculation of alveolar gradients, are identical to the VOCs in truly inhaled air. For the measurement of inhaled air and room air, two IMS, each coupled with an MCC that provided a pre-separation of the VOCs, were used in parallel. One device was used for sampling room air and the other for sampling inhaled air. Each device was coupled with a newly invented system that cleaned room air and provided a clean carrier gas, whereas formerly synthetic air had to be used as a carrier gas. In this pilot study, a healthy volunteer underwent three subsequent runs of sampling of inhaled air and simultaneous sampling and analysis of room air. Three of the selected 11 peaks (P4-unknown, P5-1-Butanol, and P9-Furan, 2-methyl-) had significantly higher intensities during inspiration than in room air, and four peaks (P1-1-Propanamine, N-(phenylmethylene), P2-2-Nonanone, P3-Benzene, 1,2,4-trimethyl-, and P11-Acetyl valeryl) had higher intensities in room air. Furthermore, four peaks (P6-Benzaldehyde, P7-Pentane, 2-methyl-, P8-Acetone, and P10-2-Propanamine) showed inconsistent differences in peak intensities between inhaled air and room air. To the best of our knowledge, this is the first study to compare simultaneous sampling of room air and inhaled air using MCC/IMS. The simultaneous measurement of inhaled air and room air showed that using room air for the calculation of alveolar gradients in breath analysis resulted in different alveolar gradient values than those obtained by measuring truly inhaled air.

分析呼出气体样本,特别是使用高灵敏度的方法,如MCC/IMS(多毛细管柱/离子迁移谱法),也可以检测到来自外源性生产的分析物。在这方面,有关于呼气的最佳解释的讨论,要么只考虑呼出气体中的挥发性有机化合物(VOCs),要么额外考虑室内空气的组成并计算肺泡梯度。然而,在分析呼出气体之前,没有数据表明室内空气中挥发性有机化合物的成分和浓度与直接吸入的空气中的成分和浓度是否相同。目前的研究旨在确定通常用于计算肺泡梯度的室内空气中的VOCs是否与实际吸入空气中的VOCs相同。为了测量吸入空气和室内空气,平行使用两个IMS,每个IMS都与MCC相结合,提供VOCs的预分离。一个装置用于采样室内空气,另一个装置用于采样吸入空气。每个设备都与一个新发明的系统相结合,该系统可以净化房间空气并提供清洁的载气,而以前必须使用合成空气作为载气。在这项初步研究中,一名健康的志愿者随后进行了三次吸入空气采样和同时对室内空气采样和分析。在所选的11个峰中,有3个峰(p4 -未知、p5 -1-丁醇和p9 -呋喃、2-甲基)在吸入时的强度显著高于室内空气,而4个峰(p1 -1-丙胺、N-(苯基亚甲基)、p2 -2-壬壬酮、p3 -苯、1,2,4-三甲基和p11 -乙酰戊酰)在室内空气中的强度更高。此外,四个峰(p6 -苯甲醛、p7 -戊烷、2-甲基、p8 -丙酮和p10 -2-丙胺)在吸入空气和室内空气之间的峰强度差异不一致。据我们所知,这是第一个比较使用MCC/IMS同时采样室内空气和吸入空气的研究。同时测量吸入空气和室内空气表明,在呼吸分析中使用室内空气计算肺泡梯度与测量真实吸入空气得到的肺泡梯度值不同。
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引用次数: 0
A low-cost internal standard loader for solid-phase sorbing tools. 用于固相吸附工具的低成本内部标准装载机。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-08-29 DOI: 10.1088/1752-7163/acef4b
F M Vivaldi, S Reale, S Ghimenti, D Biagini, A Lenzi, T Lomonaco, F Di Francesco

Solid-phase sorption is widely used for the analysis of gaseous specimens as it allows at the same time to preconcentrate target analytes and store samples for relatively long periods. The addition of internal standards (ISs) in the analytical workflow can greatly reduce the variability of the analyses and improve the reliability of the protocols. In this work, we describe the development and testing of a portable system for the reliable production of gaseous mixture of8D-Toluene in a 1L Silonite canister as well as its reproducible loading into solid-phase sorbing tools as ISs. The portable system was tested using needle trap microextraction, solid-phase extraction, and thin-film microextraction techniques commonly employed for the analysis of gaseous samples. Even though our specific interest is in breath analysis, the system can also be used for the collection of any kind of gaseous specimen. A microcontroller allows the fine control of the sampling flow by a digital mass flow controller. Flow rate and sample volume could be set either through a rotary encoder mounted onto the control board or through a dedicated android app. The variability of the airflow is in the range 5-200 ml min-1and it is lower than 1%, whereas the variability of the IS (8D-Toluene) concentration dispensed over time by the loader measured by selected-ion flow-tube mass spectrometry (MS) is <3%. This combination resulted in intra- and inter-day precision of the amount loaded in the sorbent tools lower than 15%. No carry-over was detected in the loader after the delivery of the8D-Toluene measured by gas chromatography-MS. The8D-Toluene concentration in the canister was stable for up to three weeks at room temperature.

固相吸附法广泛用于气体样品的分析,因为它同时允许对目标分析物进行预浓缩,并将样品储存相对较长的时间。在分析工作流程中加入内部标准(ISs)可以大大减少分析的可变性,提高协议的可靠性。在这项工作中,我们描述了一种便携式系统的开发和测试,该系统用于在1L硅土罐中可靠地生产8d -甲苯的气体混合物,并将其可重复加载到固相吸附工具中作为ISs。便携式系统使用针阱微萃取、固相萃取和薄膜微萃取技术进行了测试,这些技术通常用于分析气体样品。尽管我们对呼气分析感兴趣,但该系统也可用于收集任何种类的气体样本。微控制器允许通过数字质量流量控制器对采样流量进行精细控制。流速和样本量可以通过安装在控制板上的旋转编编器或通过专用的android应用程序进行设置。气流的变异性在5-200 ml min-1范围内,低于1%,而通过选择离子流管质谱(MS)测量的装载机分配的is (8d -甲苯)浓度随时间的变异性是通过气相色谱-MS测量的8d -甲苯。在室温下,罐内的8d -甲苯浓度可稳定达三周。
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引用次数: 0
Evaluation of different classification methods using electronic nose data to diagnose sarcoidosis. 利用电子鼻数据评估不同分类方法诊断结节病。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-08-29 DOI: 10.1088/1752-7163/acf1bf
Iris G van der Sar, Nynke van Jaarsveld, Imme A Spiekerman, Floor J Toxopeus, Quint L Langens, Marlies S Wijsenbeek, Justin Dauwels, Catharina C Moor

Electronic nose (eNose) technology is an emerging diagnostic application, using artificial intelligence to classify human breath patterns. These patterns can be used to diagnose medical conditions. Sarcoidosis is an often difficult to diagnose disease, as no standard procedure or conclusive test exists. An accurate diagnostic model based on eNose data could therefore be helpful in clinical decision-making. The aim of this paper is to evaluate the performance of various dimensionality reduction methods and classifiers in order to design an accurate diagnostic model for sarcoidosis. Various methods of dimensionality reduction and multiple hyperparameter optimised classifiers were tested and cross-validated on a dataset of patients with pulmonary sarcoidosis (n= 224) and other interstitial lung disease (n= 317). Best performing methods were selected to create a model to diagnose patients with sarcoidosis. Nested cross-validation was applied to calculate the overall diagnostic performance. A classification model with feature selection and random forest (RF) classifier showed the highest accuracy. The overall diagnostic performance resulted in an accuracy of 87.1% and area-under-the-curve of 91.2%. After comparing different dimensionality reduction methods and classifiers, a highly accurate model to diagnose a patient with sarcoidosis using eNose data was created. The RF classifier and feature selection showed the best performance. The presented systematic approach could also be applied to other eNose datasets to compare methods and select the optimal diagnostic model.

电子鼻技术是一种新兴的诊断应用,利用人工智能对人类呼吸模式进行分类。这些模式可用于诊断医疗状况。结节病通常是一种难以诊断的疾病,因为没有标准的程序或决定性的测试。因此,基于eNose数据的准确诊断模型可能有助于临床决策。本文的目的是评估各种降维方法和分类器的性能,以便设计一个准确的结节病诊断模型。在肺结节病(n=224)和其他间质性肺病(n=317)患者的数据集上测试并交叉验证了各种降维方法和多个超参数优化分类器。选择表现最佳的方法来创建诊断结节病患者的模型。应用嵌套交叉验证来计算整体诊断性能。具有特征选择和随机森林(RF)分类器的分类模型显示出最高的准确度。总体诊断性能的准确率为87.1%,曲线下面积为91.2%。在比较了不同的降维方法和分类器后,创建了一个使用eNose数据诊断结节病患者的高准确度模型。RF分类器和特征选择显示出最佳的性能。所提出的系统方法也可以应用于其他eNose数据集,以比较方法并选择最佳诊断模型。
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引用次数: 1
Artificial intelligence can dynamically adjust strategies for auxiliary diagnosing respiratory diseases and analyzing potential pathological relationships. 人工智能可以动态调整策略,辅助诊断呼吸系统疾病,分析潜在的病理关系。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-08-25 DOI: 10.1088/1752-7163/acf065
Quan Zhang, Binyue Chen, Guohua Liu

Respiratory diseases are one of the leading causes of human death and exacerbate the global burden of non-communicable diseases. Finding a method to assist clinicians pre-diagnose these diseases is an urgent task. Existing artificial intelligence-based methods can improve the clinical diagnosis efficiency, but still face challenges. For example, the lack of interpretability, the problem of information redundancy or missing caused by only using static data, the difficulty of model to learn the interdependence between features, and the performance of model is limited by sparse datasets, etc. To alleviate these problems, we propose a novel RQPA-Net. It consists of Q&A diagnosis module (QAD) and pathological inference module (PI). The QAD is responsible for interacting with patients, adjusting inquiry strategies dynamically and collecting effective information for disease diagnosis. The designed multi-subspace network can alleviate the problem that classical method is difficult to understand the interdependence between features. The deep reinforcement learning designed also can alleviate the problem of classical methods lack of interpretability. The PI is responsible for reasoning potential pathological relationships between diseases or symptoms based on existing knowledge. Through integrating the advantages of deep learning and reinforcement learning techniques, PI can handle sparse datasets. Finally, for auxiliary diagnosis, the model achieves 0.9780 ± 0.0002 Recall, 0.9778 ± 0.0003 Acc, 0.9779 ± 0.0003 Precision and 0.9780 ± 0.0003 F1-score on the test set. In terms of assisting pathological analysis, compared with the end-to-end model, our model achieves higher comprehensive performance on different tasks and datasets with different degrees of sparsity. Even in sparse datasets, it can effectively infer potential associations between diseases or symptoms, and has higher potential clinical application. In this paper, we propose a novel network structure, which can not only assist doctors in diagnosing diseases, but also contribute to explore the potential disease mechanisms. It provides a new perspective for integrating AI technology and clinical practice.

呼吸系统疾病是人类死亡的主要原因之一,并加剧了全球非传染性疾病的负担。寻找一种方法来帮助临床医生预先诊断这些疾病是一项紧迫的任务。现有的基于人工智能的方法可以提高临床诊断效率,但仍面临挑战。例如,缺乏可解释性,仅使用静态数据导致的信息冗余或缺失问题,模型难以学习特征之间的相互依赖关系,模型的性能受到稀疏数据集的限制等。为了解决这些问题,我们提出了一种新的RQPA-Net。它由问答诊断模块(QAD)和病理推理模块(PI)组成。QAD负责与患者互动,动态调整问诊策略,收集疾病诊断的有效信息。所设计的多子空间网络可以缓解传统方法难以理解特征间相互依赖关系的问题。所设计的深度强化学习还可以缓解经典方法缺乏可解释性的问题。PI负责根据现有知识推理疾病或症状之间潜在的病理关系。通过融合深度学习和强化学习技术的优点,PI可以处理稀疏数据集。最后,对于辅助诊断,该模型在测试集上达到了0.9780±0.0002 Recall, 0.9778±0.0003 Acc, 0.9779±0.0003 Precision和0.9780±0.0003 f1得分。在辅助病理分析方面,与端到端模型相比,我们的模型在不同任务和不同稀疏度的数据集上取得了更高的综合性能。即使在稀疏数据集中,也能有效推断疾病或症状之间的潜在关联,具有较高的临床应用潜力。在本文中,我们提出了一种新的网络结构,它不仅可以帮助医生诊断疾病,而且有助于探索潜在的疾病机制。为人工智能技术与临床实践的结合提供了新的视角。
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引用次数: 0
Breath analysis combined with cardiopulmonary exercise testing and echocardiography for monitoring heart failure patients: the AEOLUS protocol. 呼吸分析结合心肺运动试验和超声心动图监测心力衰竭患者:AEOLUS方案。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-08-09 DOI: 10.1088/1752-7163/acec08
Denise Biagini, Nicola Riccardo Pugliese, Federico Vivaldi, Silvia Ghimenti, Alessio Lenzi, Francesca De Angelis, Matyas Ripszam, Tobias Bruderer, Silvia Armenia, Federica Cappelli, Stefano Taddei, Stefano Masi, Fabio Di Francesco, Tommaso Lomonaco

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.

本文介绍了AEOLUS将呼吸分析与心肺运动试验(CPET)和超声心动图检查相结合用于监测心力衰竭(HF)患者的初步研究。前瞻性纳入10例既往临床诊断为HF并左室射血分数降低的连续患者,以及15例具有心血管危险因素(包括高血压、II型糖尿病或慢性缺血性心脏病)的对照患者。采用针阱微萃取法采集静息时和CPET联合运动应激超声心动图(CPET- ese)期间的呼气样本,并通过气相色谱-质谱联用分析。该方案还涉及使用选定的离子流管质谱仪在运动期间进行呼气异戊二烯和丙酮分析。静息时,HF患者呼吸中丙酮和戊烷水平升高,这分别与脂肪酸氧化改变和氧化应激有关。丙酮与血浆金标准生物标志物NT-proBNP之间存在显著正相关(r= 0.646,p< 0.001)。在运动过程中,一些呼出的挥发物(如异戊二烯)反映了通气和/或血流动力学的适应,而另一些(如硫化物和3-羟基-2-丁酮)则取决于它们的来源。心力衰竭患者的丙酮水平与对照组显著不同,表明心力衰竭患者的心肌和全身代谢对运动的适应发生了改变。这些初步数据表明,同时获取CPET-ESE和呼吸分析是可行的,并可能为心力衰竭患者对运动的代谢不适应提供额外的临床信息。这类信息可能有助于确定疾病恶化风险较高的患者。
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引用次数: 1
Oxylipin concentration shift in exhaled breath condensate (EBC) of SARS-CoV-2 infected patients. SARS-CoV-2 感染者呼出气体冷凝物(EBC)中的氧脂素浓度变化。
IF 3.7 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-08-07 DOI: 10.1088/1752-7163/acea3d
Eva Borras, Mitchell M McCartney, Dante E Rojas, Tristan L Hicks, Nam K Tran, Tina Tham, Maya M Juarez, Lisa Franzi, Richart W Harper, Cristina E Davis, Nicholas J Kenyon

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.

气道上皮细胞感染严重急性呼吸道冠状病毒 2(SARS-CoV-2)会导致严重的呼吸道损伤和缺氧性肺损伤。对下呼吸道进行无创采样具有挑战性,而确定一种能以无创方式收集的高代表性标本的能力将为研究 COVID-19 疾病的代谢组学后果提供机会。在本研究中,我们采用液相色谱-高分辨色谱法(LC-MS)对从住院的 COVID-19 患者(COVID+)和阴性对照组(包括非住院和因其他原因住院的患者(COVID-))收集的呼出气体冷凝物(EBC)进行了有针对性的代谢组学研究。我们能够无创识别和量化炎性氧化脂蛋白的变化和失调,最终可用于监测 COVID-19 疾病的进展或严重程度以及对治疗的反应。我们还预计基于 EBC 的生化氧脂素变化与 COVID-19 宿主对感染的反应有关。结果表明,在感染 SAR-CoV-2 的 EBC 样本与阴性对照组之间,有 10 种目标氧脂素存在显著差异。这些化合物是前列腺素 A2 和 D2、LXA4、5-HETE、12-HETE、15-HETE、5-HEPE、9-HODE、13-oxoODE 和 19(20)-EpDPA,它们与炎症和氧化应激过程相关的特定途径(即 P450、COX、15-LOX)有关。此外,所有这些化合物都被 COVID+ 上调,这意味着它们在感染 SAR-CoV-2 的受试者中浓度更高。鉴于 COVID-19 的许多症状本质上都是炎症性的,这是对该疾病病理生理学的有趣见解。对这些代谢物和其他 EBC 代谢物的呼吸监测为监测疾病进展和严重程度的关键指标提供了一个有趣的机会。
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引用次数: 0
Publisher's Note: 'Revisiting the Rationale of Mandatory Masking' (2023J. Breath Res. 4 042001). 出版者注:"重新审视强制掩蔽的理由"(2023J. 呼吸研究 4 042001)。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-08-07 DOI: 10.1088/1752-7163/acea72
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引用次数: 0
Revisiting the rationale of mandatory masking. 重新审视强制掩蔽的理由。
IF 3.8 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2023-08-07 DOI: 10.1088/1752-7163/acdf12
Jonathan D Beauchamp, Chris A Mayhew

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.

在这篇文章中,我们回顾了口罩对减少呼吸道病毒(特别是严重急性呼吸系统综合症冠状病毒 2(SARS-CoV-2))传播的有效性证据,并考虑了强制要求普遍佩戴口罩的价值,以及与此类措施相关的广泛负面影响。在 SARS-CoV-2 大流行之前,人们认为健康人戴口罩预防感染或作为病毒传播的无意载体几乎没有任何益处。这一公认的政策在疫情初期被匆忙推翻,当时世界各地区和国家都规定了严格的戴口罩要求。现在,大流行已经开始三年多了,对使用口罩减少 SARS-CoV-2(或其他病原体)传播的大量研究得出的结论基本上是不一致和相互矛盾的。目前还没有具有统计意义或明确无误的科学证据来证明强制普通健康人群佩戴口罩以减少病毒传播的合理性。即使在个别情况下戴口罩有可能减少 SARS-CoV-2 的传播,也需要权衡强制戴口罩带来的身体、心理和社会危害,更不用说无数废弃口罩进入我们脆弱的环境所造成的负面影响了。鉴于没有明确的科学证据证明口罩对减少传播有任何作用,加上使用口罩对人和环境造成的明显危害,我们认为,在一般人群中强制使用口罩是不合理的,在今后的大流行病对策政策中必须放弃。
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Journal of breath research
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