Liu Zubi, Yao Yinan, Wang Limin, Yu Yunsong, Zhou Hua
Department of Infectious Diseases, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Thorac Dis. 2025 Jul 31;17(7):5238-5249. doi: 10.21037/jtd-2025-1163. Epub 2025 Jul 29.
BACKGROUND: Pulmonary fungal infections are becoming increasingly prevalent, particularly among immunocompromised patients. Traditional culture-based and serological diagnostic methods exhibit low sensitivity and prolonged turnaround times (TATs), highlighting the need for more efficient diagnostic approaches. This study aims to evaluate the diagnostic performance of metagenomic third-generation sequencing (mTGS) using the Oxford Nanopore platform (Oxford Nanopore Technologies) for the detection of fungal pathogens in lower respiratory tract infections, and to compare its effectiveness with conventional diagnostic methods. METHODS: This study evaluated the clinical utility of mTGS with the Nanopore platform for diagnosing lower respiratory tract fungal infections (LRTFIs). Between January and August 2022, bronchoalveolar lavage fluid (BALF) samples were collected from 253 patients with suspected fungal infections across four medical centers in Hangzhou, China. Fungal detection was performed through both mTGS and conventional culture, and diagnostic performance was assessed via bioinformatics analysis and clinical adjudication. RESULTS: Fungal infections were detected in 65 samples (29.3%), with 11 fungal species identified by mTGS, including , , and . Conventional culture identified only six species, missing key pathogens such as and . mTGS demonstrated a sensitivity of 78.1% [95% confidence interval (CI): 66.0-87.5%], a specificity of 90.5% (95% CI: 84.8-94.7%), a positive predictive value (PPV) of 76.9% (95% CI: 64.8-86.5%), and a negative predictive value (NPV) of 91.1% (95% CI: 85.4-95.0%). It showed high sensitivity for (76.5%) and (82.4%) but lower sensitivity for spp. (66.7%). mTGS also co-detected viral and bacterial pathogens, offering comprehensive pathogen profiling, and significantly shortened the TATs to 7 hours as compared to 2-7 days for culture. CONCLUSIONS: mTGS on the nanopore platform offers a rapid, sensitive, and comprehensive approach for diagnosing LRTFIs, particularly in immunocompromised patients. It serves as a valuable complementary tool for detecting mixed infections or culture-negative pneumonia. However, careful interpretation is needed regarding the clinical relevance of colonizing fungi such as .
背景：肺部真菌感染日益普遍，尤其是在免疫功能低下的患者中。传统的基于培养和血清学的诊断方法灵敏度低且周转时间长，这凸显了对更高效诊断方法的需求。本研究旨在评估使用牛津纳米孔平台（牛津纳米孔技术公司）的宏基因组第三代测序（mTGS）对下呼吸道感染中真菌病原体的诊断性能，并将其有效性与传统诊断方法进行比较。 方法：本研究评估了纳米孔平台mTGS在诊断下呼吸道真菌感染（LRTFI）中的临床效用。2022年1月至8月期间，从中国杭州四个医疗中心的253例疑似真菌感染患者中收集支气管肺泡灌洗液（BALF）样本。通过mTGS和传统培养进行真菌检测，并通过生物信息学分析和临床判定评估诊断性能。 结果：在65个样本（29.3%）中检测到真菌感染，mTGS鉴定出11种真菌，包括 、 和 。传统培养仅鉴定出6种，遗漏了 和 等关键病原体。mTGS的灵敏度为78.1%[95%置信区间（CI）：66.0 - 87.5%]，特异性为90.5%（95% CI：84.8 - 94.7%），阳性预测值（PPV）为76.9%（95% CI：64.8 - 86.5%），阴性预测值（NPV）为91.1%（95% CI：85.4 - 95.0%）。它对 （76.5%）和 （82.4%）显示出高灵敏度，但对 属（66.7%）的灵敏度较低。mTGS还共同检测到病毒和细菌病原体，提供全面的病原体谱分析，与培养的2 - 7天相比，显著缩短周转时间至7小时。 结论：纳米孔平台上的mTGS为诊断LRTFI提供了一种快速、灵敏且全面的方法，尤其是在免疫功能低下的患者中。它是检测混合感染或培养阴性肺炎的有价值的补充工具。然而，对于诸如 等定植真菌的临床相关性需要谨慎解读。
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