PDF(Pubmed)
Abstract：
UNASSIGNED: An early diagnosis and treatment of invasive fungal disease (IFD) is associated with improved outcome, but the moderate sensitivity of noninvasive diagnostic tests makes this challenging. Invasive diagnostic procedures such as bronchoalveolar lavage (BAL) have a higher yield but are not without risk. The detection and sequencing of microbial cell-free DNA (mcfDNA) may facilitate a noninvasive diagnosis.
UNASSIGNED: In a prospective observational study, we collected plasma in the 120 hours preceding or following a BAL in patients with hematological malignancies suspected for a pulmonary IFD. The EORTC/MSGERC2020 criteria were used for IFD classification. Sequencing was performed by Karius (Redwood City, CA) using their Karius Test (KT) on plasma and a \"research use only test\" on BAL fluid if available. Cases with a probable/proven IFD were identified based on standard diagnostic tests on serum and BAL (microscopy, polymerase chain reaction, galactomannan, culture) and used to calculate the sensitivity, specificity, and additional diagnostic value of the KT.
UNASSIGNED: Of 106 patients enrolled, 39 (37%) had a proven/probable invasive aspergillosis, 7 (7%) a non-Aspergillus IFD, and 4 (4%) a mixed IFD. The KT detected fungal mcfDNA in 29 (28%) patients. Compared with usual diagnostic tests, the sensitivity and specificity were 44.0% (95% confidence interval [CI], 31.2-57.7) and 96.6% (95% CI, 88.5%-99.1%). Sensitivity of the KT was higher in non-Aspergillus IFD (Mucorales:2/3, Pneumocystis jirovecii: 3/5). On BAL, the sensitivity was 72.2% (95% CI, 62.1-96.3), and specificity 83.3% (95% CI, 49.1-87.5).
UNASSIGNED: Sequencing of mcfDNA may facilitate a noninvasive diagnosis of IFD in particular non-Aspergillus IFD. However, on plasma and similar to currently available diagnostics, it cannot be used as a \"rule-out\" test.
UNASSIGNED: In a prospective observational study, we collected plasma in the 120 hours preceding or following a BAL in patients with hematological malignancies suspected for a pulmonary IFD. The EORTC/MSGERC2020 criteria were used for IFD classification. Sequencing was performed by Karius (Redwood City, CA) using their Karius Test (KT) on plasma and a \"research use only test\" on BAL fluid if available. Cases with a probable/proven IFD were identified based on standard diagnostic tests on serum and BAL (microscopy, polymerase chain reaction, galactomannan, culture) and used to calculate the sensitivity, specificity, and additional diagnostic value of the KT.
UNASSIGNED: Of 106 patients enrolled, 39 (37%) had a proven/probable invasive aspergillosis, 7 (7%) a non-Aspergillus IFD, and 4 (4%) a mixed IFD. The KT detected fungal mcfDNA in 29 (28%) patients. Compared with usual diagnostic tests, the sensitivity and specificity were 44.0% (95% confidence interval [CI], 31.2-57.7) and 96.6% (95% CI, 88.5%-99.1%). Sensitivity of the KT was higher in non-Aspergillus IFD (Mucorales:2/3, Pneumocystis jirovecii: 3/5). On BAL, the sensitivity was 72.2% (95% CI, 62.1-96.3), and specificity 83.3% (95% CI, 49.1-87.5).
UNASSIGNED: Sequencing of mcfDNA may facilitate a noninvasive diagnosis of IFD in particular non-Aspergillus IFD. However, on plasma and similar to currently available diagnostics, it cannot be used as a \"rule-out\" test.
摘要：
■侵袭性真菌病（IFD）的早期诊断和治疗与改善预后相关，但是非侵入性诊断测试的中等敏感性使得这具有挑战性.侵入性诊断程序，如支气管肺泡灌洗（BAL）具有较高的产量，但并非没有风险。微生物无细胞DNA（mcfDNA）的检测和测序可以促进非侵入性诊断。
■在一项前瞻性观察性研究中，我们收集了疑似肺部IFD的血液系统恶性肿瘤患者在BAL之前或之后120小时内的血浆.EORTC/MSGERC2020标准用于IFD分类。测序由Karius（红木城，CA）对血浆使用Karius测试（KT），并对BAL液进行“仅研究使用测试”（如果可用）。根据血清和BAL的标准诊断测试（显微镜检查，聚合酶链反应，半乳甘露聚糖,文化)并用于计算灵敏度，特异性，和KT的额外诊断价值。
■在参加的106名患者中，39人（37%）患有已证实/可能的侵袭性曲霉病，7（7%）一非曲霉IFD，和4(4%)混合IFD。KT在29例（28％）患者中检测到真菌mcfDNA。与通常的诊断测试相比，敏感性和特异性为44.0%(95%置信区间[CI]，31.2-57.7）和96.6%（95%CI，88.5%-99.1%）。在非曲霉IFD中，KT的敏感性更高（Mucorales：2/3，肺孢子虫：3/5）。在BAL上,敏感性为72.2%（95%CI，62.1-96.3），特异性83.3%（95%CI，49.1-87.5）。
■mcfDNA的测序可以促进IFD特别是非曲霉IFD的非侵入性诊断。然而,在等离子体和类似于目前可用的诊断，它不能用作“排除”测试。
■在一项前瞻性观察性研究中，我们收集了疑似肺部IFD的血液系统恶性肿瘤患者在BAL之前或之后120小时内的血浆.EORTC/MSGERC2020标准用于IFD分类。测序由Karius（红木城，CA）对血浆使用Karius测试（KT），并对BAL液进行“仅研究使用测试”（如果可用）。根据血清和BAL的标准诊断测试（显微镜检查，聚合酶链反应，半乳甘露聚糖,文化)并用于计算灵敏度，特异性，和KT的额外诊断价值。
■在参加的106名患者中，39人（37%）患有已证实/可能的侵袭性曲霉病，7（7%）一非曲霉IFD，和4(4%)混合IFD。KT在29例（28％）患者中检测到真菌mcfDNA。与通常的诊断测试相比，敏感性和特异性为44.0%(95%置信区间[CI]，31.2-57.7）和96.6%（95%CI，88.5%-99.1%）。在非曲霉IFD中，KT的敏感性更高（Mucorales：2/3，肺孢子虫：3/5）。在BAL上,敏感性为72.2%（95%CI，62.1-96.3），特异性83.3%（95%CI，49.1-87.5）。
■mcfDNA的测序可以促进IFD特别是非曲霉IFD的非侵入性诊断。然而,在等离子体和类似于目前可用的诊断，它不能用作“排除”测试。
