Metagenomic next-generation sequencing and galactomannan testing for the diagnosis of invasive pulmonary aspergillosis

Abstract

To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) and galactomannan (GM) testing in invasive pulmonary aspergillosis (IPA) and to compare mNGS with other diagnostic approaches (serum/bronchoalveolar lavage fluid (BALF)-GM and conventional microbiological tests (CMTs) including sputum smears and culture, BALF fungal culture, and bronchial brushing). In all, 237 patients were enrolled in this retrospective study, including 120 patients with IPA and 117 with non-IPA pulmonary infections treated at Henan Provincial People's Hospital between June 2021 and February 2024. The diagnostic performance of mNGS was compared to conventional diagnostic methods including serum GM, BALF-GM, sputum smear microscopy, sputum culture, bronchial brushings, and BALF culture. The proportion of patients with underlying diseases was significantly higher in the IPA group than in the non-IPA group (P < 0.05). Compared to conventional diagnostic methods for IPA, mNGS showed higher diagnostic efficacy, with a sensitivity of 92.5% and a specificity of 94.02%. The area under the receiver operating characteristic curve (AUC) for BALF-GM for diagnosing IPA was 0.8, with an optimal cutoff value of 0.546, sensitivity of 66.7%, and specificity of 82.1%. The combination of mNGS and BALF-GM testing further improved diagnostic performance (sensitivity of 96.67% and specificity of 78.63%). mNGS testing has excellent diagnostic efficacy for IPA, which is further enhanced by combining it with BALF-GM testing. This approach has considerable potential for the early diagnosis and targeted treatment of IPA.

Keywords: Bronchoalveolar lavage fluid; Diagnostic performance; Galactomannan; Invasive pulmonary aspergillosis; Metagenomic next-generation sequencing.

Fig. 1

ROC curve of serum GM and BALF-GM testing for diagnosing IPA. IPA, invasive pulmonary aspergillosis; ROC, receiver operating characteristic; GM, galactomannan antigen; BALF, bronchoalveolar lavage fluid; AUC, area under curve.

Fig. 2

ROC curve of BALF-GM or/and mNGS testing for diagnosing IPA. IPA, invasive pulmonary aspergillosis; ROC, receiver operating characteristic; GM, galactomannan antigen; BALF, bronchoalveolar lavage fluid; AUC, area under curve (AUC).