Xu Chun-Hui, Zhang Li-Ning, Liu Teng, Zhu Guo-Qing, Fan Yu-Ping, Chen Xin, Shen Yu-Yan, Yu Yue-Tian, Shi Yuan-Yuan, Jiang Er-Lie, Feng Si-Zhou
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China; Tianjin Institutes of Health Science, Tianjin, 301600, China; Microbiology laboratory, Tianjin Union Precision Medical Diagnostic Co., Ltd, Tianjin, 301617, China.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China; Tianjin Institutes of Health Science, Tianjin, 301600, China.
J Microbiol Immunol Infect. 2025 Jun 7. doi: 10.1016/j.jmii.2025.06.001.
BACKGROUND/PURPOSE(S): Invasive pulmonary aspergillosis (IPA) is a serious fungal infection, and its diagnosis is diverse, especially in patients with hematological disorders. This study aims to determine the optimal diagnostic strategy for IPA in such patients by comparing various microbiological tests.
A total of 490 blood and 138 bronchoalveolar lavage fluid (BALF) samples collected from 182 IPA and 407 no-IPA patients (based on EORTC/MSGERC criteria) were retrospectively analyzed by metagenomic next-generation sequencing (mNGS), Aspergillus-PCR, and galactomannan (GM) (enzyme immunoassay [EIA] and lateral flow assay [LFA]).
In BALF samples, GM-EIA, GM-LFA, Aspergillus-PCR, and mNGS showed sensitivities of 68.1 %, 53.2 %, 83.0 %, and 59.6 %-all higher than in blood (43.7 %, 34.4 %, 51.7 %, 55.0 %). In blood samples, mNGS had the highest sensitivity (71.9 %) in neutropenic patients, which was further improved when combined with GM-EIA (77.1 %). In non-neutropenic patients, Aspergillus-PCR was the most sensitive assay (47.3 %), with sensitivity improving to 56.4 % when combined with GM-EIA. Blood test sensitivities were lower in patients with prolonged antifungal therapy (≥7 days) vs. <7 days (Aspergillus-PCR: 38.6 % vs. 57.0 %; mNGS: 31.8 % vs. 64.5 %; GM-EIA: 27.3 % vs. 50.5 %; all P < 0.05), with no impact on BALF results.
BALF is critical for accurate IPA diagnosis, particularly in patients with prior antifungal therapy. BALF Aspergillus-PCR offers optimal sensitivity, while blood-based mNGS and PCR are recommended for neutropenic and non-neutropenic patients, respectively. Combining molecular methods with GM testing enhances diagnostic performances. Tailored strategies are essential to improve early detection and clinical outcomes in high-risk hematologic populations.
背景/目的：侵袭性肺曲霉病（IPA）是一种严重的真菌感染，其诊断方法多样，尤其是在血液系统疾病患者中。本研究旨在通过比较各种微生物学检测方法，确定此类患者中IPA的最佳诊断策略。
对从182例IPA患者和407例非IPA患者（基于欧洲癌症研究与治疗组织/侵袭性真菌感染协作组标准）收集的490份血液样本和138份支气管肺泡灌洗（BALF）液样本进行回顾性分析，采用宏基因组下一代测序（mNGS）、曲霉PCR和半乳甘露聚糖（GM）（酶免疫测定法[EIA]和侧向流动分析法[LFA]）。
在BALF样本中，GM-EIA、GM-LFA、曲霉PCR和mNGS的敏感性分别为68.1%、53.2%、83.0%和59.6%，均高于血液样本（43.7%、34.4%、51.7%、55.0%）。在血液样本中，mNGS在中性粒细胞减少患者中敏感性最高（71.9%），与GM-EIA联合使用时进一步提高（77.1%）。在非中性粒细胞减少患者中，曲霉PCR是最敏感的检测方法（47.3%），与GM-EIA联合使用时敏感性提高到56.4%。接受延长抗真菌治疗（≥7天）的患者血液检测敏感性低于治疗时间<7天的患者（曲霉PCR：38.6%对57.0%；mNGS：31.8%对64.5%；GM-EIA：27.3%对50.5%；均P<0.05），但对BALF结果无影响。
BALF对准确诊断IPA至关重要，尤其是在接受过抗真菌治疗的患者中。BALF曲霉PCR具有最佳敏感性，而对于中性粒细胞减少和非中性粒细胞减少患者，分别推荐基于血液的mNGS和PCR检测。将分子方法与GM检测相结合可提高诊断性能。制定针对性策略对于改善高危血液系统人群的早期检测和临床结局至关重要。
