{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:44:20Z","timestamp":1793659460329,"version":"4.5.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    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\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    , for which mNGS performed better than antigen detection.\n                    <jats:italic>S. pneumoniae<\/jats:italic>\n                    , cytomegalovirus and\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2023.1220943","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T09:57:53Z","timestamp":1695722273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Metagenomic next-generation sequencing of bronchoalveolar lavage fluid assists in the diagnosis of pathogens associated with lower respiratory tract infections in children"],"prefix":"10.3389","volume":"13","author":[{"given":"Yunjian","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueting","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanlin","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongping","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.3201\/eid2406.171612","article-title":"Human endophthalmitis caused by pseudorabies virus infection, China 2017","volume":"24","author":"Ai","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1099\/jmmcr.0.005117","article-title":"Multi-system manifestations of Mycoplasma pneumoniae infection in a young patient","volume":"4","author":"Al Busaidi","year":"2017","journal-title":"JMM Case Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3562","DOI":"10.1128\/JCM.00767-12","article-title":"Microbiome diversity in the bronchial tracts of patients with chronic obstructive pulmonary disease","volume":"50","author":"Cabrera-Rubio","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.541092","article-title":"Application of metagenomic next-generation sequencing in the diagnosis of pulmonary infectious pathogens from bronchoalveolar lavage samples","volume":"11","author":"Chen","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1080\/22221751.2020.1725399","article-title":"RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak","volume":"9","author":"Chen","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"B6","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/s41576-019-0113-7","article-title":"Clinical metagenomics","volume":"20","author":"Chiu","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4345","DOI":"10.3791\/4345","article-title":"Bronchoalveolar lavage (BAL) for research; obtaining adequate sample yield","volume":"28","author":"Collins","year":"2014","journal-title":"J. Vis. Exp. JoVE"},{"key":"B8","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.jare.2021.09.012","article-title":"Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections","volume":"38","author":"Diao","year":"2021","journal-title":"J. Adv. Res."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2021.100874","article-title":"Thalassemia and autoimmune diseases: absence of evidence or evidence of absence","volume":"52","author":"El Hasbani","year":"2022","journal-title":"Blood Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e01888","DOI":"10.1128\/mBio.01888-15","article-title":"Making the leap from research laboratory to clinic: challenges and opportunities for next-generation sequencing in infectious disease diagnostics","volume":"6","author":"Goldberg","year":"2015","journal-title":"mBio"},{"key":"B11","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1146\/annurev-pathmechdis-012418-012751","article-title":"Clinical metagenomic next-generation sequencing for pathogen detection","volume":"14","author":"Gu","year":"2019","journal-title":"Annu. Rev. Pathol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1080\/17476348.2020.1806063","article-title":"Bronchoalveolar lavage: role in the evaluation of pulmonary interstitial disease","volume":"14","author":"Hogea","year":"2020","journal-title":"Expert Rev. Respir. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"567","DOI":"10.2147\/IDR.S235182","article-title":"Metagenomic next-generation sequencing versus traditional pathogen detection in the diagnosis of peripheral pulmonary infectious lesions","volume":"13","author":"Huang","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"B14","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1056\/NEJMoa1500245","article-title":"Community-acquired pneumonia requiring hospitalization among U.S. Adults","volume":"373","author":"Jain","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1097\/INF.0b013e31812e4b81","article-title":"Comparison of polymerase chain reaction and the indirect particle agglutination antibody test for the diagnosis of Mycoplasma pneumoniae pneumonia in children during two outbreaks","volume":"26","author":"Kim","year":"2007","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"E12353","DOI":"10.1073\/pnas.1809700115","article-title":"Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults","volume":"115","author":"Langelier","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B17","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1164\/rccm.201706-1097LE","article-title":"Metagenomic sequencing detects respiratory pathogens in hematopoietic cellular transplant patients","volume":"197","author":"Langelier","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1186\/s12890-021-01756-4","article-title":"Usefulness of procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) levels in the differential diagnosis of acute bacterial, viral, and mycoplasmal respiratory tract infections in children","volume":"21","author":"Li","year":"2021","journal-title":"BMC Pulm. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/s10096-019-03734-5","article-title":"Application of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in critically ill patients","volume":"39","author":"Li","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1080\/00365549850160954","article-title":"Evaluation of Meridian ImmunoCard Mycoplasma test for the detection of Mycoplasma pneumoniae-specific IgM in paediatric patients","volume":"30","author":"Matas","year":"1998","journal-title":"Scand. J. Infect. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"S231","DOI":"10.1093\/cid\/ciy693","article-title":"Microbiological diagnostic performance of metagenomic next-generation sequencing when applied to clinical practice","volume":"67","author":"Miao","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1101\/gr.238170.118","article-title":"Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid","volume":"29","author":"Miller","year":"2019","journal-title":"Genome Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"602.e1","DOI":"10.1016\/j.ajog.2018.02.012","article-title":"The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology","volume":"218","author":"Moreno","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00023","article-title":"Classification of extrapulmonary manifestations due to mycoplasma pneumoniae infection on the basis of possible pathogenesis","volume":"7","author":"Narita","year":"2016","journal-title":"Front. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1007\/s15010-021-01615-8","article-title":"C-reactive protein and procalcitonin for antimicrobial stewardship in COVID-19","volume":"49","author":"Pink","year":"2021","journal-title":"Infection"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.567615","article-title":"Improving pulmonary infection diagnosis with metagenomic next generation sequencing","volume":"10","author":"Qian","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1039\/c8an01488d","article-title":"A review of methods for the detection of pathogenic microorganisms","volume":"144","author":"Rajapaksha","year":"2019","journal-title":"Analyst"},{"key":"B28","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.cppeds.2013.10.003","article-title":"Multiple organ dysfunction syndrome","volume":"43","author":"Ram\u00edrez","year":"2013","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"B29","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1086\/421997","article-title":"Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis","volume":"39","author":"Simon","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.critrevonc.2018.10.003","article-title":"Congenital neutropenia and primary immunodeficiency diseases","volume":"133","author":"Spoor","year":"2019","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/cei.13119","article-title":"The role of the immune system in kidney disease","volume":"192","author":"Tecklenborg","year":"2018","journal-title":"Clin. Exp. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e284","DOI":"10.1016\/S2666-5247(21)00304-9","article-title":"Lower respiratory tract infections in children requiring mechanical ventilation: a multicentre prospective surveillance study incorporating airway metagenomics","volume":"3","author":"Tsitsiklis","year":"2022","journal-title":"Lancet Microbe"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1056\/NEJMoa1401268","article-title":"Actionable diagnosis of neuroleptospirosis by next-generation sequencing","volume":"370","author":"Wilson","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"B34","unstructured":"The top 10 causes of death2020"},{"key":"B35","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1016\/j.ijid.2022.07.062","article-title":"Patients with infectious diseases undergoing mechanical ventilation in the intensive care unit have better prognosis after receiving metagenomic next-generation sequencing assay","volume":"122","author":"Xi","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01488-22","article-title":"Application of metagenomic next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) in diagnosing pneumonia of children","volume":"10","author":"Yang","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"B37","doi-asserted-by":"publisher","first-page":"446","DOI":"10.3988\/jcn.2016.12.4.446","article-title":"Detection of listeria monocytogenes in CSF from three patients with meningoencephalitis by next-generation sequencing","volume":"12","author":"Yao","year":"2016","journal-title":"J. Clin. Neurol. Seoul Korea"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.33","article-title":"The human lung microbiome\u2014A hidden link between microbes and human health and diseases","volume":"1","author":"Yi","year":"2022","journal-title":"iMeta"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-10-48","article-title":"Difference of clinical features in childhood Mycoplasma pneumoniae pneumonia","volume":"10","author":"Youn","year":"2010","journal-title":"BMC Pediatr."},{"key":"B40","doi-asserted-by":"publisher","first-page":"126","DOI":"10.3324\/haematol.2021.278413","article-title":"Predicting response of severe aplastic anemia to immunosuppression combined with eltrombopag","volume":"107","author":"Zaimoku","year":"2022","journal-title":"Haematologica"},{"key":"B41","doi-asserted-by":"publisher","first-page":"5512","DOI":"10.1021\/acs.analchem.8b00399","article-title":"Detection of pathogenic microorganisms by microfluidics based analytical methods","volume":"90","author":"Zhang","year":"2018","journal-title":"Anal. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1093\/cid\/ciy802","article-title":"Pulmonary metagenomic sequencing suggests missed infections in immunocompromised children","volume":"68","author":"Zinter","year":"2019","journal-title":"Clin. Infect. Dis."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1220943\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T09:57:58Z","timestamp":1695722278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1220943\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":42,"alternative-id":["10.3389\/fcimb.2023.1220943"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1220943","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,26]]},"article-number":"1220943"}}