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

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RESEARCH ARTICLE

Open Access

Optimal specimen type for accurate diagnosis of infectious peripheral pulmonary lesions by mNGS Qing Wang1,2†, Bo Wu3†, Donglin Yang4, Chao Yang2, Zhixian Jin2*, Jie Cao1 and Jing Feng1*

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. Keywords: Infectious peripheral pulmonary lesions, Metagenomic next-generation sequencing (mNGS), Transbronchial lung biopsy (TBLB), Bronchoalveolar lavage fluid (BALF), And bronchial needle brushing

Background Infectious diseases are the most common cause of death worldwide [1]. Pulmonary infections result in more deaths each year than any other type of infectious disease [2]. Delayed identification of the causative pathogen is the major cause of treatment failure and death in cases * Correspondence: [email protected]; [email protected] † Qing Wang and Bo Wu contributed equally to this work. 2 Respiratory Department of Kunming Municipal First People’s Hospital, Kunming 650000, China 1 Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China Full list of author information is available at the end of the article

of pulmonary infection. Current microbiological tests such as culture-based methods have limitations in terms of sensitivity [3, 4], speed, and the spectrum of available assay targets [5]. Failure to identify the etiologic agent can lead to nonspecific and ineffective antibiotic therapy, resulting in adverse outcomes [5, 6]. Timely identification of infectious pathogens allows tailoring of antimicrobial regimens, which can improve the prognosis of pulmonary infections. Advances in genomic sequencing technologies and bioinformatics approaches have provided useful tools for clinical d