Department of Infectious Disease, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China.
Department of Clinical Laboratory, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China.
Front Cell Infect Microbiol. 2022 Sep 8;12:1008924. doi: 10.3389/fcimb.2022.1008924. eCollection 2022.
This 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.
A 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).
A 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.
This metabolomic approach using UHPLC-HRMS could be used as a noninvasive method for the diagnosis of PA.
本研究旨在确定肺部曲霉菌病（PA）患者呼出气冷凝液（EBC）样本的独特代谢谱，并探讨其在 PA 诊断中的应用价值。
共纳入 133 例患者，包括 66 例 PA 患者（侵袭性肺曲霉病，n=3；慢性肺曲霉病，n=60；变应性支气管肺曲霉病，n=3）和对照组（n=67）。采用超高效液相色谱-高分辨质谱联用技术（UHPLC-HRMS）分析 EBC 样本。对 22 例慢性肺曲霉病患者在治疗过程中不同时间点（治疗前、<1 个月、1-2 个月、2-3 个月、3-6 个月和≥6 个月）采集的 EBC 样本进行代谢谱分析。采用聚类分析、Venn 图和受试者工作特征分析（ROC）评估潜在生物标志物。
在 EBC 样本中检测到 47 种有潜在意义的代谢物。进一步研究表明， Asperpyrone C、Kotanin、Terphenyllin、Terrelumamide B 和 Cyclotryprostatin D 可作为 PA 的诊断生物标志物。PA 患者和对照组 EBC 样本代谢谱的分类较好，PA 患者的灵敏度为 100%，特异性为 89.6%。这些候选生物标志物的 Venn 图分析显示了三种主要类型的化合物，可进一步区分曲霉肿和慢性空洞性 PA。此外，抗真菌治疗对 EBC 结果的价值影响有限。
本研究采用 UHPLC-HRMS 的代谢组学方法可作为一种非侵入性方法用于 PA 的诊断。
