breath test

呼气试验
  • 文章类型: Case Reports
    该病例报告研究了一次功能神经病学对诊断为乳糖不耐受的35岁女性患者的影响。患者出现严重的胃肠道症状,包括频繁的腹泻,腹胀,在食用乳制品时呕吐。干预措施旨在重置可能导致她病情的功能失调的神经系统计划。该研究利用标准化的乳糖不耐受呼气测试来测量治疗前后不同间隔的氢气和甲烷水平。治疗后结果显示症状缓解,患者报告排便正常,没有先前的症状。尽管有这些改进,生化标志物在较高的时间点(150和175分钟)治疗后保持与治疗前的值相似,表明持续的乳糖吸收不良,并突出氢测量的可变性。该病例报告表明,一次功能神经病学可以显着缓解乳糖不耐受的症状。然而,这些结果的初步性质强调了需要进一步研究,包括更大的样本量和长期随访,以充分了解治疗的疗效和潜在机制。
    This case report examines the impact of a single session of functional neurology on a 35-year-old female patient diagnosed with lactose intolerance. The patient presented with severe gastrointestinal symptoms, including frequent diarrhea, bloating, and vomiting upon dairy consumption. The intervention aimed to reset dysfunctional neurological programs believed to contribute to her condition. The study utilized a standardized lactose intolerance breath test to measure the hydrogen and methane levels at various intervals before and after treatment. Post-treatment results showed symptomatic relief with the patient reporting normalized bowel movements and the absence of previous symptoms. Despite these improvements, the biochemical markers at higher time points (150 and 175 min) post-treatment remained similar to the pre-treatment values, indicating persistent lactose malabsorption and highlighting the variability of hydrogen measurements. This case report suggests that a single session of functional neurology can significantly alleviate the symptoms of lactose intolerance. However, the preliminary nature of these results underscores the need for further research involving larger sample sizes and long-term follow-up to fully understand the treatment\'s efficacy and underlying mechanisms.
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  • 文章类型: Journal Article
    呼吸分析,尽管是一种被忽视的生物基质,有丰富的疾病诊断史。然而,挥发性有机化合物(VOCs)尚未确立自己作为特定疾病的临床验证的生物标志物。由于仅关注晚期或恶性疾病的生物标志物在临床实践中可能具有有限的相关性,本综述的目的是探讨VOC呼气试验诊断非癌症疾病的潜力:(1)胃食管反流病(GERD)和Barrett食管(BE)等癌前疾病,呼气试验可以补充内窥镜筛查;(2)与自身炎症和菌群失调相关的腔内疾病,如炎症性肠病(IBD),肠易激综合征(IBS),和乳糜泻,目前依赖于活检和基于症状的诊断;(3)慢性肝病,如肝硬化,肝性脑病,和非酒精性脂肪性肝病,缺乏用于疾病进展监测和预后评估的非侵入性诊断工具。通过EMBASE进行了文献检索,MEDLINE,和Cochrane数据库,概述了24项研究。这些研究的特点,包括分析平台,无序类型和阶段,组大小,并讨论了诊断测试的性能评估参数。此外,探讨了如何将VOC用作非侵入性诊断工具来补充现有的黄金标准。通过改进研究设计,取样程序,比较尿液和血液中的挥发性有机化合物,我们可以更深入地了解VOCs的代谢途径。这将建立呼吸分析作为鉴别诊断和疾病监测的有效非侵入性方法。
    Breath analysis, despite being an overlooked biomatrix, has a rich history in disease diagnosis. However, volatile organic compounds (VOCs) have yet to establish themselves as clinically validated biomarkers for specific diseases. As focusing solely on late-stage or malignant disease biomarkers may have limited relevance in clinical practice, the objective of this review is to explore the potential of VOC breath tests for the diagnosis of non-cancer diseases: (1) Precancerous conditions like gastro-esophageal reflux disease (GERD) and Barrett\'s esophagus (BE), where breath tests can complement endoscopic screening; (2) endoluminal diseases associated with autoinflammation and dysbiosis, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and coeliac disease, which currently rely on biopsy and symptom-based diagnosis; (3) chronic liver diseases like cirrhosis, hepatic encephalopathy, and non-alcoholic fatty liver disease, which lack non-invasive diagnostic tools for disease progression monitoring and prognostic assessment. A literature search was conducted through EMBASE, MEDLINE, and Cochrane databases, leading to an overview of 24 studies. The characteristics of these studies, including analytical platforms, disorder type and stage, group size, and performance evaluation parameters for diagnostic tests are discussed. Furthermore, how VOCs can be utilized as non-invasive diagnostic tools to complement existing gold standards is explored. By refining study designs, sampling procedures, and comparing VOCs in urine and blood, we can gain a deeper understanding of the metabolic pathways underlying VOCs. This will establish breath analysis as an effective non-invasive method for differential diagnosis and disease monitoring.
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  • 文章类型: Journal Article
    小肠细菌过度生长(SIBO)是小肠的一种病理,可能使个体容易遭受各种营养缺乏。关于SIBO的特定亚型是否鲜为人知,如氢占优势(H+),甲烷占优势(M+),或氢/甲烷占优势(H+/M+),影响SIBO患者的营养状况和饮食摄入。这项研究的目的是研究生化参数之间可能的相关性,膳食营养素摄入量,和不同的SIBO亚型。这项观察性研究包括67例新诊断为SIBO的患者。生化参数和饮食研究利用实验室测试和食物记录,分别。H+/M+组血清维生素D水平低(p<0.001),低血清铁蛋白(p=0.001)和低纤维摄入量(p=0.001)。M+组与高血清叶酸(p=0.002)、低纤维(p=0.001)和低乳糖(p=0.002)相关。H+组与低乳糖摄入相关(p=0.027)。这些结果表明,SIBO的亚型可能对饮食摄入有不同的影响,导致一系列生化缺陷。相反,特定的饮食模式可能会导致SIBO亚型的发展。营养状况和饮食的评估,随着SIBO亚型的诊断,被认为是SIBO治疗的关键组成部分。
    Small intestinal bacterial overgrowth (SIBO) is a pathology of the small intestine and may predispose individuals to various nutritional deficiencies. Little is known about whether specific subtypes of SIBO, such as the hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane-dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p < 0.001), low serum ferritin (p = 0.001) and low fiber intake (p = 0.001). The M+ group was correlated with high serum folic acid (p = 0.002) and low intakes of fiber (p = 0.001) and lactose (p = 0.002). The H+ group was associated with low lactose intake (p = 0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of biochemical deficiencies. Conversely, specific dietary patterns may predispose one to the development of a SIBO subtype. The assessment of nutritional status and diet, along with the diagnosis of SIBO subtypes, are believed to be key components of SIBO therapy.
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  • 文章类型: Journal Article
    背景:用电子鼻(e-nose)分析呼出的挥发性有机化合物(VOC)在医学诊断中作为一种非侵入性,快,和敏感的疾病检测和监测方法。这项研究调查了肺活量测定或体育锻炼等活动是否会影响哮喘患者和健康个体的呼出VOC测量,电子鼻技术临床应用验证的关键步骤。 方法:该研究分析了27名健康个体和27名稳定期哮喘患者使用电子鼻的呼出的VOCs,在进行肺活量测定和爬五层楼梯之前和之后。使用经过验证的技术收集呼吸样品,并用Cyranose320电子鼻进行分析。 结果:在健康对照中,肺功能检查和运动后,呼出VOC谱均保持不变.在哮喘患者中,主成分分析和随后的判别分析显示,肺活量测定后存在显著差异(与基线66.7%交叉验证精度[CVA],p<0.05)和运动(vs.基线70.4%CVA,p<0.05)。 结论:健康个体的电子鼻测量结果是一致的,不受肺活量测定或体育锻炼的影响。然而,在哮喘患者中,活动后检测到呼出的挥发性有机化合物的显著变化,指示可能由于收缩或炎症引起的气道反应,强调电子鼻在呼吸系统疾病诊断和监测方面的潜力。 .
    Analyzing exhaled volatile organic compounds (VOCs) with an electronic nose (e-nose) is emerging in medical diagnostics as a non-invasive, quick, and sensitive method for disease detection and monitoring. This study investigates if activities like spirometry or physical exercise affect exhaled VOCs measurements in asthmatics and healthy individuals, a crucial step for e-nose technology\'s validation for clinical use. The study analyzed exhaled VOCs using an e-nose in 27 healthy individuals and 27 patients with stable asthma, before and after performing spirometry and climbing five flights of stairs. Breath samples were collected using a validated technique and analyzed with a Cyranose 320 e-nose. In healthy controls, the exhaled VOCs spectrum remained unchanged after both lung function test and exercise. In asthmatics, principal component analysis and subsequent discriminant analysis revealed significant differences post-spirometry (vs. baseline 66.7% cross validated accuracy [CVA],p< 0.05) and exercise (vs. baseline 70.4% CVA,p< 0.05). E-nose measurements in healthy individuals are consistent, unaffected by spirometry or physical exercise. However, in asthma patients, significant changes in exhaled VOCs were detected post-activities, indicating airway responses likely due to constriction or inflammation, underscoring the e-nose\'s potential for respiratory condition diagnosis and monitoring.
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  • 文章类型: Journal Article
    在糖酵解过程中,葡萄糖分子的C3碳成为丙酮酸分子的C1碳,葡萄糖分子的C1和C2碳在三羧酸(TCA)循环中代谢。利用葡萄糖分子中C原子的位置依赖性代谢,[1-13C],[2-13C],和[3-13C]葡萄糖呼气试验用于评估葡萄糖代谢。然而,慢性乙醇消费的影响仍未完全了解。因此,我们使用[1-13C]评估了乙醇喂养大鼠的葡萄糖代谢,[2-13C],和[3-13C]葡萄糖呼气试验。乙醇喂养(ERs)和对照大鼠(CRs)(每个n=8)用于本研究,和ER通过用16%乙醇溶液代替饮用水来制备。我们给药100mg/kg的[1-13C],[2-13C],或[3-13C]葡萄糖给大鼠,并收集呼出的空气(间隔10分钟,180分钟)。我们比较了通过IR同位素比率光谱法测得的呼吸的13CO2水平(Δ13CO2,‰)以及ERs和CRs之间的13CO2水平-时间曲线的曲线下面积(AUC)值。[1-13C]葡萄糖和[2-13C]葡萄糖给药后的13CO2水平和AUC在ERs中低于CRs。相反,[3-13C]葡萄糖呼气试验的AUC显示ERs和CRs之间没有显着差异,尽管在110-120分钟的时间间隔内,ERs中的13CO2水平明显较高。这些发现表明,长期消耗乙醇会减少葡萄糖氧化,而不会同时减少糖酵解。我们的研究证明了13C标记的葡萄糖呼气测试作为评估各种受试者葡萄糖代谢的非侵入性和可重复方法的实用性。包括酗酒或糖尿病患者。
    The C3 carbon of glucose molecules becomes the C1 carbon of pyruvate molecules during glycolysis, and the C1 and C2 carbons of glucose molecules are metabolized in the tricarboxylic acid (TCA) cycle. Utilizing this position-dependent metabolism of C atoms in glucose molecules, [1-13C], [2-13C], and [3-13C]glucose breath tests are used to evaluate glucose metabolism. However, the effects of chronic ethanol consumption remain incompletely understood. Therefore, we evaluated glucose metabolism in ethanol-fed rats using [1-13C], [2-13C], and [3-13C]glucose breath tests. Ethanol-fed (ERs) and control rats (CRs) (n = 8 each) were used in this study, and ERs were prepared by replacing drinking water with a 16% ethanol solution. We administered 100 mg/kg of [1-13C], [2-13C], or [3-13C]glucose to rats and collected expired air (at 10-min intervals for 180 min). We compared the 13CO2 levels (Δ13CO2, ‰) of breath measured by IR isotope ratio spectrometry and area under the curve (AUC) values of the 13CO2 levels-time curve between ERs and CRs. 13CO2 levels and AUCs after administration of [1-13C]glucose and [2-13C]glucose were lower in ERs than in CRs. Conversely, the AUC for the [3-13C]glucose breath test showed no significant differences between ERs and CRs, although 13CO2 levels during the 110-120 min interval were significantly high in ERs. These findings indicate that chronic ethanol consumption diminishes glucose oxidation without concomitantly reducing glycolysis. Our study demonstrates the utility of 13C-labeled glucose breath tests as noninvasive and repeatable methods for evaluating glucose metabolism in various subjects, including those with alcoholism or diabetes.
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  • 文章类型: Journal Article
    核酸扩增测试(NAAT)被认为是COVID-19诊断的金标准。这些测试需要专业的人力和设备,长时间的处理和拭子取样对患者来说是不愉快的。在COVID-19患者的呼吸中已经鉴定出几种挥发性有机化合物(VOC)。使用呼气测试检测这些VOC可以帮助快速识别COVID-19患者。
    评估“健康呼吸”(BOH)COVID-19基于傅立叶变换红外(FTIR)光谱的呼吸测试的准确性。
    使用Tedlar袋收集具有NAAT结果的有或没有COVID-19症状的患者的呼吸样本,并使用BOHFTIR光谱进行盲目分析。BOH同时测量几种挥发性有机化合物,区分阳性和阴性结果。将BOH结果与NAAT结果作为金标准进行比较。
    分析了531名患者的呼吸样本。BOH呼气试验的敏感性为79.5%,特异性为87.2%。阳性预测值(PPV)为74.7%,阴性预测值(NPV)为90.0%。计算准确率为84.8%,曲线下面积为0.834。亚组分析显示,无呼吸道症状患者的NPV优于有症状患者的NPV(94.7%vs80.7%,P值<0.0001),有呼吸道症状的患者的PPV高于无症状个体的PPV(85.3%vs69.2%,P值0.0196)。
    我们发现BOHCOVID-19呼气试验对患者友好,快速,具有高准确率和NPV的非侵入性诊断测试可以有效排除COVID-19,特别是在预测试概率低的个体中。
    UNASSIGNED: Nucleic acid amplification tests (NAAT) are considered the gold standard for COVID-19 diagnosis. These tests require professional manpower and equipment, long processing and swab sampling which is unpleasant to the patients. Several volatile organic compounds (VOCs) have been identified in the breath of COVID-19 patients. Detection of these VOCs using a breath test could help rapidly identify COVID-19 patients.
    UNASSIGNED: Assess the accuracy of \'Breath of Health\' (BOH) COVID-19 Fourier-transform infra-red (FTIR) Spectroscopy-based breath test.
    UNASSIGNED: Breath samples from patients with or without symptoms suggestive for COVID-19 who had NAAT results were collected using Tedlar bags and were blindly analysed using BOH FTIR spectroscopy. BOH Measures several VOCs simultaneously and differentiating positive and negative results. BOH results were compared to NAAT results as gold standard.
    UNASSIGNED: Breath samples from 531 patients were analysed. The sensitivity of BOH breath test was found to be 79.5% and specificity was 87.2%. Positive predictive value (PPV) was 74.7% and negative predictive value (NPV) 90.0%. Calculated accuracy rate was 84.8% and area under the curve 0.834. Subgroup analysis revealed that the NPV of patients without respiratory symptoms was superior over the NPV of symptomatic patients (94.7% vs 80.7%, P-value < 0.0001) and PPV of patients with respiratory symptoms outranks the PPV of individuals without symptoms (85.3% vs 69.2%, P-value 0.0196).
    UNASSIGNED: We found BOH COVID-19 breath test to be a patient-friendly, rapid, non-invasive diagnostic test with high accuracy rate and NPV that could efficiently rule out COVID-19 especially among individuals with low pre-test probability.
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  • 文章类型: Journal Article
    尽管实施了拯救生命的新生儿筛查计划和半乳糖限制饮食,许多经典半乳糖血症患者会出现长期衰弱的神经功能缺损和原发性卵巢功能不全。以前,我们表明,主要在GalT基因捕获的小鼠肝脏中表达的人GALTmRNA的给药增加了肝脏GALT活性的表达,不仅减少了肝脏中的半乳糖-1磷酸(gal-1P),而且减少了外周组织。由于每个外周组织需要不同的方法来检查生物标志物和/或GALT效应,这凸显了采用替代策略评估治疗总体影响的必要性.在这项研究中,我们确定全身半乳糖氧化(WBGO)是一种强大的,非侵入性,以及评估旨在恢复半乳糖血症小鼠模型中GALT活性的两种基于基因的实验性疗法的体内药代动力学和药效学参数的具体方法。尽管我们的结果说明了AAVrh10介导的GALT基因转移的长期疗效,我们发现主要针对肝脏的GALTmRNA治疗足以维持WBGO。后者可能在设计新型靶向治疗以确保最佳疗效和安全性方面具有重要意义。
    Despite the implementation of lifesaving newborn screening programs and a galactose-restricted diet, many patients with classic galactosemia develop long-term debilitating neurological deficits and primary ovarian insufficiency. Previously, we showed that the administration of human GALT mRNA predominantly expressed in the GalT gene-trapped mouse liver augmented the expression of hepatic GALT activity, which decreased not only galactose-1 phosphate (gal-1P) in the liver but also peripheral tissues. Since each peripheral tissue requires distinct methods to examine the biomarker and/or GALT effect, this highlights the necessity for alternative strategies to evaluate the overall impact of therapies. In this study, we established that whole-body galactose oxidation (WBGO) as a robust, noninvasive, and specific method to assess the in vivo pharmacokinetic and pharmacodynamic parameters of two experimental gene-based therapies that aimed to restore GALT activity in a mouse model of galactosemia. Although our results illustrated the long-lasting efficacy of AAVrh10-mediated GALT gene transfer, we found that GALT mRNA therapy that targets the liver predominantly is sufficient to sustain WBGO. The latter could have important implications in the design of novel targeted therapy to ensure optimal efficacy and safety.
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  • 文章类型: Journal Article
    人体通过组织和各种体液或呼出的气体释放出大量的挥发性有机化合物(VOC)。这些化合物共同创造了独特的化学特征,它可以潜在地用于识别与结直肠癌(CRC)相关的人类代谢变化,因此,有助于这种疾病的诊断。这项研究的主要目的是调查和表征与CRC患者和对照组呼吸相关的VOCs化学模式,并确定该疾病的潜在呼气标志物。为此,采用气相色谱-质谱联用技术。总的来说,在由152名受试者提供的呼吸样品中鉴定出1656种不同的化合物。22个具有统计学意义的VOCs(对二甲苯;己醛;2-甲基-1,3-二氧戊环;2,2,4-三甲基-1,3-戊二醇二异丁酸酯;十六烷;壬烷;乙苯;环己酮;邻苯二甲酸二乙酯;6-甲基-5-庚烯-2-酮;四氢-2H-吡喃-2-酮;2-丁酮;在十二烷苯甲1CRC患者呼吸中这些VOC水平的升高表明这些化合物有可能作为CRC的生物标志物。
    The human body emits a multitude of volatile organic compounds (VOCs) via tissues and various bodily fluids or exhaled breath. These compounds collectively create a distinctive chemical profile, which can potentially be employed to identify changes in human metabolism associated with colorectal cancer (CRC) and, consequently, facilitate the diagnosis of this disease. The main goal of this study was to investigate and characterize the VOCs\' chemical patterns associated with the breath of CRC patients and controls and identify potential expiratory markers of this disease. For this purpose, gas chromatography-mass spectrometry was applied. Collectively, 1656 distinct compounds were identified in the breath samples provided by 152 subjects. Twenty-two statistically significant VOCs (p-xylene; hexanal; 2-methyl-1,3-dioxolane; 2,2,4-trimethyl-1,3-pentanediol diisobutyrate; hexadecane; nonane; ethylbenzene; cyclohexanone; diethyl phthalate; 6-methyl-5-hepten-2-one; tetrahydro-2H-pyran-2-one; 2-butanone; benzaldehyde; dodecanal; benzothiazole; tetradecane; 1-dodecanol; 1-benzene; 3-methylcyclopentyl acetate; 1-nonene; toluene) were observed at higher concentrations in the exhaled breath of the CRC group. The elevated levels of these VOCs in CRC patients\' breath suggest the potential for these compounds to serve as biomarkers for CRC.
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  • 文章类型: Journal Article
    目的:肥胖是小肠细菌过度生长(SIBO)的诱发因素。这项研究的目的是前瞻性评估SIBO的患病率及其临床,生物,以及Roux-en-Y胃旁路术(RYGB)手术之前和之后24个月的营养方面。
    方法:在2016年至2020年间,51例患者(平均BMI为46.9kg/m2,66.7%的女性)需要RYGB。每个病人都接受了葡萄糖呼气测试,功能性消化体征的标准化审讯,饮食调查,验血,一张fecalogram,和人体测量数据收集。这些研究在手术前和RYGB后1、3、6、9、12、18和24个月进行。
    结果:手术前,我们发现SIBO的患病率为17.6%(95%CI=[8.9%;31.4%]).在RYGB之后,在24个月的随访结束时,89.5%的患者发生SIBO。手术后肛门失禁似乎非常频繁,影响18.8%的人口在手术后18个月。尽管饮食脂质存在显着限制,但手术后我们观察到脂肪泻呈阳性,平均脂质为11.1g/24小时(p=0.0282)。
    结论:我们的研究证实了文献中关于SIBO在重度肥胖患者中患病率的数据。第一次,我们观察到RYGB后SIBO突然出现,呼气试验中呼出的氢与脂肪代谢图上的脂质吸收不良之间存在相关性。因此,这些患者会出现脂肪性腹泻,经常大便失禁。
    OBJECTIVE: Obesity is a predisposing factor for small intestinal bacterial overgrowth (SIBO). The aim of this study was to prospectively evaluate the prevalence of SIBO as well as its clinical, biological, and nutritional aspects before and up to 24 months after a Roux-en-Y gastric bypass (RYGB) surgery.
    METHODS: Fifty-one patients (mean BMI 46.9 kg/m2, 66.7% women) requesting RYGB were included between 2016 and 2020. Each patient underwent a glucose breath test, a standardized interrogation on functional digestive signs, a dietary survey, a blood test, a fecalogram, and anthropometric data gathering. These investigations were carried out before surgery and at 1, 3, 6, 9, 12, 18, and 24 months after RYGB.
    RESULTS: Before surgery, we found a prevalence of 17.6% of SIBO (95% CI = [8.9%; 31.4%]). After RYGB, at the end of 24 months of follow-up, 89.5% of patients developed SIBO. Anal incontinence appeared to be very frequent after surgery, affecting 18.8% of our population 18 months after surgery. We observed positive steatorrhea after surgery with an average of 11.1 g of lipids/24 h despite a significant limitation of dietary lipids (p = 0.0282).
    CONCLUSIONS: Our study corroborates data in the literature on the prevalence of SIBO in severe obesity patients. For the first time, we observed the sudden appearance of SIBO after RYGB, with a correlation between exhaled hydrogen on a breath test and lipid malabsorption on the fecalogram. As a result, these patients develop fatty diarrhea, with frequent fecal incontinence.
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  • 文章类型: Journal Article
    呼气分析,特别强调挥发性有机化合物,由于其明显优于其他诊断测试,因此代表了临床研究的增长领域。已经广泛研究了许多病理学以通过代谢组学鉴定呼出物中的特定生物标志物。然而,呼气测试向诊所的转移仍然有限,主要是由于方法标准化的不足。关键步骤包括选择呼吸样本类型,收集装置,和富集技术。GC-MS是分析呼气中挥发性有机化合物的参考分析技术,尤其是在代谢组学的生物标志物发现阶段。这篇综述全面审查和比较了专注于癌症的代谢组学研究,肺部疾病,和传染病。除了深入研究报道的实验设计,它还提供了方法论方面的批判性讨论,从实验设计和样品收集到潜在病理特异性生物标志物的鉴定。
    Exhaled breath analysis, with particular emphasis on volatile organic compounds, represents a growing area of clinical research due to its obvious advantages over other diagnostic tests. Numerous pathologies have been extensively investigated for the identification of specific biomarkers in exhalates through metabolomics. However, the transference of breath tests to clinics remains limited, mainly due to deficiency in methodological standardization. Critical steps include the selection of breath sample types, collection devices, and enrichment techniques. GC-MS is the reference analytical technique for the analysis of volatile organic compounds in exhalates, especially during the biomarker discovery phase in metabolomics. This review comprehensively examines and compares metabolomic studies focusing on cancer, lung diseases, and infectious diseases. In addition to delving into the experimental designs reported, it also provides a critical discussion of the methodological aspects, ranging from the experimental design and sample collection to the identification of potential pathology-specific biomarkers.
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