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非中性粒细胞减少症患者肺部曲霉菌病的宏基因组下一代测序诊断:一项回顾性研究。

Metagenomic next-generation sequencing for the diagnosis of pulmonary aspergillosis in non-neutropenic patients: a retrospective study.

机构信息

Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Naval Medical University, Shanghai, China.

出版信息

Front Cell Infect Microbiol. 2022 Aug 1;12:925982. doi: 10.3389/fcimb.2022.925982. eCollection 2022.

DOI:10.3389/fcimb.2022.925982
PMID:35979088
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9376315/
Abstract

This study aimed to obtain further in-depth information on the value of metagenomic next-generation sequencing (mNGS) for diagnosing pulmonary aspergillosis in non-neutropenic patients. We did a retrospective study, in which 33 non-neutropenic patients were included, of which 12 were patients with pulmonary aspergillosis and 21 were diagnosed with non-pulmonary aspergillosis. Fungi and all other co-pathogens in bronchoalveolar lavage fluid (BALF) (27 cases), blood (6 cases), and/or pleural fluid (1 case) samples were analyzed using mNGS. One of the patients submitted both BALF and blood samples. We analyzed the clinical characteristics, laboratory tests, and radiologic features of pulmonary aspergillosis patients and compared the diagnostic accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value of mNGS with conventional etiological methods and serum (1,3)-β-D-glucan. We also explored the efficacy of mNGS in detecting mixed infections and co-pathogens. We further reviewed modifications of antimicrobial therapy for patients with pulmonary aspergillosis according to the mNGS results. Finally, we compared the detection of in BALF and blood samples from three patients using mNGS. In non-neutropenic patients, immunocompromised conditions of non-pulmonary aspergillosis were far less prevalent than in patients with pulmonary aspergillosis. More patients with pulmonary aspergillosis received long-term systemic corticosteroids (50% vs. 14.3%, p < 0.05). Additionally, mNGS managed to reach a sensitivity of 91.7% for diagnosing pulmonary aspergillosis, which was significantly higher than that of conventional etiological methods (33.3%) and serum (1,3)-β-D-glucan (33.3%). In addition, mNGS showed superior performance in discovering co-pathogens (84.6%) of pulmonary aspergillosis; bacteria, bacteria-fungi, and bacteria-PJP-virus were most commonly observed in non-neutropenic patients. Moreover, mNGS results can help guide effective treatments. According to the mNGS results, antimicrobial therapy was altered in 91.7% of patients with pulmonary aspergillosis. The diagnosis of detected in blood samples, which can be used as a supplement to BALF samples, seemed to show a higher specificity than that in BALF samples. mNGS is a useful and effective method for the diagnosis of pulmonary aspergillosis in non-neutropenic patients, detection of co-pathogens, and adjustment of antimicrobial treatment.

摘要

本研究旨在进一步深入了解宏基因组下一代测序(mNGS)在诊断非中性粒细胞减少症患者肺部曲霉病中的价值。我们进行了一项回顾性研究,纳入了 33 名非中性粒细胞减少症患者,其中 12 名患者患有肺部曲霉病,21 名患者诊断为非肺部曲霉病。使用 mNGS 分析了支气管肺泡灌洗液(BALF)(27 例)、血液(6 例)和/或胸腔液(1 例)样本中的真菌和所有其他共病原体。其中一名患者同时提交了 BALF 和血液样本。我们分析了肺部曲霉病患者的临床特征、实验室检查和影像学特征,并比较了 mNGS 与传统病因学方法和血清(1,3)-β-D-葡聚糖的诊断准确性,包括敏感性、特异性、阳性预测值和阴性预测值。我们还探讨了 mNGS 检测混合感染和共病原体的效果。我们进一步根据 mNGS 结果修改了肺部曲霉病患者的抗菌治疗方案。最后,我们比较了三名患者的 BALF 和血液样本中 的检测结果。在非中性粒细胞减少症患者中,非肺部曲霉病的免疫功能低下情况远少于肺部曲霉病患者。更多的肺部曲霉病患者接受了长期的全身皮质类固醇治疗(50%比 14.3%,p<0.05)。此外,mNGS 对肺部曲霉病的诊断灵敏度达到 91.7%,明显高于传统病因学方法(33.3%)和血清(1,3)-β-D-葡聚糖(33.3%)。此外,mNGS 在发现肺部曲霉病的共病原体方面表现出更好的性能(84.6%);细菌、细菌-真菌和细菌-PJP-病毒在非中性粒细胞减少症患者中最常见。此外,mNGS 结果可帮助指导有效治疗。根据 mNGS 结果,91.7%的肺部曲霉病患者改变了抗菌治疗方案。血液样本中检测到的 ,可作为 BALF 样本的补充,其特异性似乎高于 BALF 样本。mNGS 是一种有用且有效的方法,可用于诊断非中性粒细胞减少症患者的肺部曲霉病、检测共病原体以及调整抗菌治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cee/9376315/4394ff46a2bd/fcimb-12-925982-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cee/9376315/d4667847440e/fcimb-12-925982-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cee/9376315/4394ff46a2bd/fcimb-12-925982-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cee/9376315/d4667847440e/fcimb-12-925982-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cee/9376315/4394ff46a2bd/fcimb-12-925982-g002.jpg

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