Metagenomic next-generation sequencing of bronchoalveolar lavage fluid assists in the diagnosis of pathogens associated with lower respiratory tract infections in children

Yunjian Xu; Yueting Jiang; Yan Wang; Fanlin Meng; Wenyan Qin; Yongping Lin

doi:10.3389/fcimb.2023.1220943

Metagenomic next-generation sequencing of bronchoalveolar lavage fluid assists in the diagnosis of pathogens associated with lower respiratory tract infections in children

Front Cell Infect Microbiol. 2023 Sep 26:13:1220943. doi: 10.3389/fcimb.2023.1220943. eCollection 2023.

Authors

Yunjian Xu¹, Yueting Jiang¹, Yan Wang², Fanlin Meng², Wenyan Qin², Yongping Lin^{1

3}

Affiliations

¹ Department of Clinical Laboratory, The Key Laboratory of Advanced Interdisciplinary Studies Center, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou, China.
² CapitalBio Technology Inc., Beijing, China.
³ Department of Laboratory Medicine, Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, China.

Abstract

Worldwide, lower respiratory tract infections (LRTI) are an important cause of hospitalization in children. Due to the relative limitations of traditional pathogen detection methods, new detection methods are needed. The purpose of this study was to evaluate the value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) samples for diagnosing children with LRTI based on the interpretation of sequencing results. A total of 211 children with LRTI admitted to the First Affiliated Hospital of Guangzhou Medical University from May 2019 to December 2020 were enrolled. The diagnostic performance of mNGS versus traditional methods for detecting pathogens was compared. The positive rate for the BALF mNGS analysis reached 95.48% (95% confidence interval [CI] 92.39% to 98.57%), which was superior to the culture method (44.07%, 95% CI 36.68% to 51.45%). For the detection of specific pathogens, mNGS showed similar diagnostic performance to PCR and antigen detection, except for Streptococcus pneumoniae, for which mNGS performed better than antigen detection. S. pneumoniae, cytomegalovirus and Candida albicans were the most common bacterial, viral and fungal pathogens. Common infections in children with LRTI were bacterial, viral and mixed bacterial-viral infections. Immunocompromised children with LRTI were highly susceptible to mixed and fungal infections. The initial diagnosis was modified based on mNGS in 29.6% (37/125) of patients. Receiver operating characteristic (ROC) curve analysis was performed to predict the relationship between inflammation indicators and the type of pathogen infection. BALF mNGS improves the sensitivity of pathogen detection and provides guidance in clinical practice for diagnosing LRTI in children.

Keywords: bronchoalveolar lavage fluid; children; lower respiratory tract infections; medication adjustment; metagenomic next-generation sequencing; pathogen diagnosis; traditional methods.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacteriophages*
Bronchoalveolar Lavage Fluid
Child
High-Throughput Nucleotide Sequencing
Humans
Metagenomics
Respiratory Tract Infections* / diagnosis
Sensitivity and Specificity
Streptococcus pneumoniae

Grants and funding

This study were funded by the project of Guangdong Dengfeng Hospital specialist team construction (No. 310139). This study was also funded by the Guangzhou Science and Technology Project (No. 2023A03J0363).