Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, and Manchester Academic Health Science Centre and National Institute for Health Research Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
Department of Respiratory Medicine, Amsterdam UMC-location AMC, University of Amsterdam, Amsterdam, The Netherlands.
Clin Infect Dis. 2023 Mar 21;76(6):1059-1066. doi: 10.1093/cid/ciac859.
Early and accurate recognition of respiratory pathogens is crucial to prevent increased risk of mortality in critically ill patients. Microbial-derived volatile organic compounds (mVOCs) in exhaled breath could be used as noninvasive biomarkers of infection to support clinical diagnosis.
In this study, we investigated the diagnostic potential of in vitro-confirmed mVOCs in the exhaled breath of patients under mechanical ventilation from the BreathDx study. Samples were analyzed by thermal desorption-gas chromatography-mass spectrometry.
Pathogens from bronchoalveolar lavage (BAL) cultures were identified in 45 of 89 patients and Staphylococcus aureus was the most commonly identified pathogen (n = 15). Of 19 mVOCs detected in the in vitro culture headspace of 4 common respiratory pathogens (S. aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli), 14 were found in exhaled breath samples. Higher concentrations of 2 mVOCs were found in the exhaled breath of patients infected with S. aureus compared to those without (3-methylbutanal: P < .01, area under the receiver operating characteristic curve [AUROC] = 0.81-0.87; and 3-methylbutanoic acid: P = .01, AUROC = 0.79-0.80). In addition, bacteria identified from BAL cultures that are known to metabolize tryptophan (E. coli, Klebsiella oxytoca, and Haemophilus influenzae) were grouped and found to produce higher concentrations of indole compared to breath samples with culture-negative (P = .034) and other pathogen-positive (P = .049) samples.
This study demonstrates the capability of using mVOCs to detect the presence of specific pathogen groups with potential to support clinical diagnosis. Although not all mVOCs were found in patient samples within this small pilot study, further targeted and qualitative investigation is warranted using multicenter clinical studies.
早期准确识别呼吸道病原体对于降低危重症患者的死亡率至关重要。微生物衍生的挥发性有机化合物(mVOCs)可作为感染的非侵入性生物标志物,辅助临床诊断。
本研究纳入了机械通气患者的呼气样本,这些患者均来自于 BreathDx 研究。样本经热解吸-气相色谱-质谱法进行分析。
45 例 89 例患者的支气管肺泡灌洗液(BAL)培养物中鉴定出病原体,最常见的病原体是金黄色葡萄球菌(n = 15)。在 4 种常见呼吸道病原体(金黄色葡萄球菌、铜绿假单胞菌、肺炎克雷伯菌和大肠埃希菌)的体外培养物气腔中共检测到 19 种 mVOCs,其中 14 种在呼气样本中被发现。与未感染金黄色葡萄球菌的患者相比,感染金黄色葡萄球菌患者的呼气样本中 2 种 mVOCs 的浓度更高(3-甲基丁醛:P<0.01,受试者工作特征曲线下面积[AUROC]为 0.81-0.87;3-甲基丁酸:P=0.01,AUROC 为 0.79-0.80)。此外,从 BAL 培养物中鉴定出的已知代谢色氨酸的细菌(大肠埃希菌、产酸克雷伯菌和流感嗜血杆菌)被分为一组,与培养物阴性(P=0.034)和其他病原体阳性(P=0.049)样本相比,它们产生的吲哚浓度更高。
本研究证明了使用 mVOCs 来检测特定病原体群的存在具有潜力,可能有助于临床诊断。尽管在本小型试点研究中并非所有 mVOCs 均在患者样本中被发现,但仍需使用多中心临床研究进行进一步的靶向和定性研究。