The clinical value of metagenomic next generation sequencing in the diagnosis of non-neutropenic invasive pulmonary aspergillosis

Background: This study aims to explore the performance of metagenomic next generation sequencing (mNGS) in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) and its clinical application value. Methods: This multi-center study enrolled 293 suspected IPA patients who conducted mNGS from October 2020 to February 2024. These cases were classified into IPA group and non-IPA group according to IPA diagnostic criteria. We analyzed the diagnostic value of mNGS by comparing with sputum culture, BALF culture, serum and BALF GM test. Results: (2.7%). The sensitivity of bronchoalveolar lavage fluid (BALF) mNGS was significantly higher than BALF culture (81.9% vs. 27.0%, p<0.001) and BALF galactomannan (GM) (81.9% vs. 55.8% (GM≥1.0 cutoff value), p<0.001). The specificity of BALF mNGS was 92.2%, which was similar with BALF culture (98.5%) and BALF GM (94.7%). The combination of BALF mNGS and GM could increase the sensitivity to 88.7%, and had great negative predictive value (NPV, 92.3%). The sensitivity of blood mNGS was significantly higher than serum GM (58.8% vs. 16.7%, p<0.001). And the sensitivity of sputum mNGS was 66.7%, which was significantly higher than sputum culture (30.0%, p=0.025). Conclusion: mNGS demonstrated significant diagnostic value for IPA, exhibiting significantly higher sensitivity compared to current conventional microbiological tests while maintaining equivalent specificity. The combination of BALF mNGS with GM performed great sensitivity and negative predictive value. BALF specimens seemed to be superior to blood and sputum samples. However, for patients unable to undergo bronchoscopy, sputum and blood mNGS were still superior to other methods.