Optimal specimen type for accurate diagnosis of infectious peripheral pulmonary lesions by mNGS

Abstract Background Reports on the application of metagenomic next-generation sequencing (mNGS) to the diagnosis of peripheral pulmonary lesions (PPLs) are scarce. There have been no studies investigating the optimal specimen type for mNGS. Methods We used mNGS to detect pathogens in matched transbronchial lung biopsy (TBLB), bronchoalveolar lavage fluid (BALF), and bronchial needle brushing (BB) specimens from 39 patients suspected of having infectious PPLs. We explored differences in microbial composition and diagnostic accuracy of mNGS for the 3 specimen types. Results mNGS was more sensitive than conventional culture for detection of bacteria and fungi in TBLB, BALF, and BB specimens, with no difference in the sensitivity of mNGS across the different specimen types. mNGS showed higher sensitivity for fungi or uncategorized pulmonary pathogens in TBLB+BALF+BB compared to TBLB but not BALF or BB specimens. There were no significant differences between the 3 specimen types in the relative abundance of pathogens, or between TBLB and BB specimens in the relative abundance of 6 common lower respiratory tract commensals. Conclusions mNGS has a higher sensitivity than the conventional culture method for detecting pathogens in TBLB, BALF, or BB specimens. mNGS of BB samples is a less invasive alternative to TBLB for the diagnosis of infectious PPLs.