血液病患者肺部真菌感染的宏基因组下一代测序诊断价值：一项多中心回顾性研究

Abstract

Using mNGS, suspected pathogens were detected in 85.2% of the samples from patients with suspected pulmonary infection, and fungi were detected in 32.5%. • The AUC for BALF-mNGS was 0.731. PB-mNGS may provide a non-invasive option to explore the etiology of PFI when bronchoscopy is not feasible,with an AUC of 7.717. • Among 166 mNGS tests from 156 possible PFI patients, fungi were detected in 130 tests (78.3%). • Prior azole prophylaxis was associated with false-negative fungal mNGS results, whereas neutropenia was associated with increased mNGS positivity. • mNGS findings informed antifungal therapy decisions, including treatment escalation (19.6%), de-escalation (9.3%), and initiation of targeted therapy (2.5%). Objectives : To evaluate the diagnostic value, clinical application and potential utility of metagenomic next-generation sequencing (mNGS) for pulmonary fungal infections (PFI) in patients with haematological diseases. Methods : A total of 994 patients with haematological diseases and suspected pulmonary infection were included, comprising 514 bronchoalveolar lavage fluid (BALF)-mNGS and 499 peripheral blood (PB)-mNGS tests. Clinical characteristics, diagnostic performance, false-negative factors, antifungal treatment modification and outcomes were analysed. Results : Based on the 2020 revised EORTC/ MSGERC criteria, 210 patients were classified as PFI, 156 as possible PFI and 628 as non-PFI. For BALF-mNGS, the diagnostic performance for PFI showed an AUC of 0.731, with a sensitivity of 72% and specificity of 74%. For PB-mNGS, the diagnostic performance for PFI showed an AUC of 0.717, with a sensitivity of 63% and specificity of 80%. Among the 156 patients classified as possible PFI (166 mNGS tests), fungi were detected by 130 tests (78.3%). Azole prophylaxis (OR, 2.42; P=0.038) were associated with false-negative mNGS results, whereas neutropenia was associated with fewer false-negative results (OR, 0.33; P=0.012). After mNGS reporting, antifungal th