{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:59:37Z","timestamp":1790657977032,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"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:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Lower respiratory tract infections (LRTI) remain a leading cause of pediatric hospitalization, yet distinguishing infection from non-infectious airway conditions and identifying the causative pathogen remains a clinical challenge. While bronchoscopy with bronchoalveolar lavage provides direct lower airway sampling, the clinical value of routine bronchoalveolar lavage fluid (BALF) cellular analysis beyond its conventional diagnostic use remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study included hospitalized children with LRTI who underwent bronchoscopy with BALF cellular analysis and targeted next-generation sequencing, as well as children with foreign-body (FB) aspiration as a noninfectious reference group. First, BALF cellular profiles were compared across three pathogen-defined LRTI subgroups: typical bacterial, viral, and\n                      <jats:italic>Mycoplasma pneumoniae<\/jats:italic>\n                      (MP). Second, multivariable linear regression analyses were performed to identify clinical, laboratory, radiologic, and bronchoscopic correlates of BALF cellular composition. Finally, secondary logistic regression analyses were performed to assess the potential clinical utility of BALF cellular composition for identifying LRTI using FB as a reference group and for discriminating typical bacterial LRTI from nontypical bacterial LRTI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 488 children with LRTI, BALF cellular composition differed across pathogen-defined groups, with MP infection showing the most pronounced neutrophil-skewed profile. Higher pathogen burden was independently associated with a more neutrophil-skewed BALF profile, whereas mucus plugs were positively associated with ln(Neu\/Mph) in pooled interaction models but showed heterogeneous directions in pathogen-specific models. Exploratory analyses suggested limited species-level variation within the bacterial and viral categories. In secondary analyses, BALF cellular composition showed good discrimination between LRTI and noninfectious group, but provided no significant incremental discrimination for typical bacterial versus nontypical bacterial LRTI when added to clinical variables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BALF cellular composition showed distinct pathogen-associated patterns in pediatric LRTIs, with MP infection exhibiting the most pronounced neutrophil-skewed profile. Higher pathogen burden was associated with a more neutrophil-skewed profile, while mucus-plug associations were sensitive to model specification. BALF cellular composition discriminated LRTI from noninfectious airway conditions but added no significant discrimination for typical bacterial versus nontypical bacterial LRTI beyond clinical variables.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1946336","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:40:08Z","timestamp":1790656808000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["BALF cellular composition in pediatric LRTI: from pathogen-specific patterns to clinical correlates"],"prefix":"10.3389","volume":"16","author":[{"given":"Fen","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiapeng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiangTeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Boai Hospital of Zhongshan","place":["Zhongshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishen","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiujun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shengjing Hospital of China Medical University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.22494","article-title":"Causes of death among infants and children in the Child Health and Mortality Prevention Surveillance (CHAMPS) Network","volume":"6","author":"Bassat","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"B2","doi-asserted-by":"publisher","first-page":"bcr2016217524","DOI":"10.1136\/bcr-2016-217524","article-title":"Disseminated adenovirus infection causing severe ARDS","volume":"2017","author":"Campbell","year":"2017","journal-title":"BMJ Case Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3892\/mmr.2024.13277","article-title":"Clinical diagnostic value of targeted next-generation sequencing for infectious diseases (Review)","volume":"30","author":"Chen","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097346","article-title":"Usefulness of cellular analysis of bronchoalveolar lavage fluid for predicting the etiology of pneumonia in critically ill patients","volume":"9","author":"Choi","year":"2014","journal-title":"PloS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"4991","DOI":"10.21037\/jtd-20-651","article-title":"Bronchoalveolar lavage as a diagnostic procedure: a review of known cellular and molecular findings in various lung diseases","volume":"12","author":"Davidson","year":"2020","journal-title":"J. Thorac. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e849","DOI":"10.1002\/iid3.849","article-title":"Analysis of cytokine levels, cytological findings, and MP\u2010DNA level in bronchoalveolar lavage fluid of children with Mycoplasma pneumoniae pneumonia","volume":"11","author":"Deng","year":"2023","journal-title":"Immun. Inflammation Dis."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/470825","article-title":"Influenza A\/H1N1 severe pneumonia: novel morphocytological findings in bronchoalveolar lavage","volume":"2014","author":"Faverio","year":"2014","journal-title":"Interdiscip. Perspect. Infect. Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.humpath.2021.04.010","article-title":"Comprehensive evaluation of bronchoalveolar lavage from patients with severe COVID-19 and correlation with clinical outcomes","volume":"113","author":"Gelarden","year":"2021","journal-title":"Hum. Pathol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.chest.2024.07.166","article-title":"BAL fluid cellular analysis and radiologic patterns in patients with fibrotic interstitial lung disease","volume":"167","author":"Grant-Orser","year":"2025","journal-title":"Chest"},{"key":"B10","doi-asserted-by":"publisher","first-page":"210241","DOI":"10.1183\/16000617.0241-2021","article-title":"Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy","volume":"31","author":"Keir","year":"2022","journal-title":"Eur. Respir. Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"00883-2020","DOI":"10.1183\/23120541.00883-2020","article-title":"Phagocyte extracellular traps in children with neutrophilic airway inflammation","volume":"7","author":"King","year":"2021","journal-title":"ERJ Open Res."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2021.106534","article-title":"Prognostic significance of bronchoalveolar lavage cellular analysis in patients with acute exacerbation of interstitial lung disease","volume":"186","author":"Kono","year":"2021","journal-title":"Respir. Med."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/17534666251393075","article-title":"Clinical implications of bronchoalveolar lavage fluid cellular analysis in fibrotic interstitial lung disease combined with CT quantification","volume":"19","author":"Lee","year":"2025","journal-title":"Ther. Adv. Respir. Dis."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1496088","article-title":"Diagnostic test accuracy of cellular analysis of bronchoalveolar lavage fluid in distinguishing pulmonary infectious and non-infectious diseases in patients with pulmonary shadow","volume":"11","author":"Li","year":"2024","journal-title":"Front. Med. (Lausanne)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1038\/s41591-020-0901-9","article-title":"Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19","volume":"26","author":"Liao","year":"2020","journal-title":"Nat. Med."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI186889","article-title":"Cellular and molecular features of asthma mucus plugs provide clues about their formation and persistence","volume":"135","author":"Liegeois","year":"2025","journal-title":"J. Clin. Invest."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1546730","article-title":"Local and systemic cytokine profiles in children with pneumonia-associated lung consolidation","volume":"16","author":"Lin","year":"2025","journal-title":"Front. Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1165\/rcmb.2020-0168OC","article-title":"Neutrophil extracellular traps increase airway mucus viscoelasticity and slow mucus particle transit","volume":"64","author":"Linssen","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.1373","article-title":"Distinct clinical characteristics of bocavirus and Mycoplasma pneumoniae infection in children plastic bronchitis","volume":"12","author":"Liu","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"4351","DOI":"10.1007\/s00431-024-05700-6","article-title":"The correlation between the level of cellular classification in bronchoalveolar lavage fluid of children with severe Mycoplasma pneumoniae and clinical characteristics","volume":"183","author":"Ma","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2100829","DOI":"10.1183\/13993003.00829-2021","article-title":"Acute respiratory distress syndrome is associated with impaired alveolar macrophage efferocytosis","volume":"58","author":"Mahida","year":"2021","journal-title":"Eur. Respir. J."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170501","article-title":"Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting","volume":"133","author":"Malainou","year":"2023","journal-title":"J. Clin. Invest."},{"key":"B23","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1136\/adc.88.10.922","article-title":"Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis","volume":"88","author":"McNamara","year":"2003","journal-title":"Arch. Dis. Child"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1164\/rccm.201202-0320ST","article-title":"An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease","volume":"185","author":"Meyer","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1007\/s00431-023-05366-6","article-title":"Childhood community-acquired pneumonia","volume":"183","author":"Meyer Sauteur","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"B26","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/nri1785","article-title":"Neutrophils and immunity: challenges and opportunities","volume":"6","author":"Nathan","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.894644","article-title":"Neutrophil recruitment in pneumococcal pneumonia","volume":"12","author":"Palmer","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1023978","article-title":"Cellular analysis and metagenomic next-generation sequencing of bronchoalveolar lavage fluid in the distinction between pulmonary non-infectious and infectious disease","volume":"12","author":"Pan","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/dc.22951","article-title":"Parainfluenza virus-3-induced cytopathic effects on lung tissue and bronchoalveolar lavage fluid in a bone marrow transplant recipient: a case report","volume":"42","author":"Pokharel","year":"2014","journal-title":"Diagn. Cytopathol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.it.2011.06.008","article-title":"Neutrophils cascading their way to inflammation","volume":"32","author":"Sadik","year":"2011","journal-title":"Trends Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/irv.12911","article-title":"Epidemiology of acute lower respiratory tract infection hospitalizations in Thai children: A 5-year national data analysis","volume":"16","author":"Sitthikarnkha","year":"2022","journal-title":"Influenza Other Respir. Viruses"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.3390\/biom11081065","article-title":"Neutrophil elastase and chronic lung disease","volume":"11","author":"Voynow","year":"2021","journal-title":"Biomolecules"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1007\/s00431-022-04761-9","article-title":"Clinical features and risk factors of plastic bronchitis caused by refractory Mycoplasma pneumoniae pneumonia in children: a practical nomogram prediction model","volume":"182","author":"Zhang","year":"2023","journal-title":"Eur. J. Pediatr."},{"key":"B34","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s41590-024-02072-9","article-title":"Robust mucosal SARS-CoV-2-specific T cells effectively combat COVID-19 and establish polyfunctional resident memory in patient lungs","volume":"26","author":"Zhu","year":"2025","journal-title":"Nat. Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e2405087","DOI":"10.1002\/advs.202405087","article-title":"Accurate diagnosis of lower respiratory infections using host response and respiratory microbiome from a single metatranscriptome test of bronchoalveolar lavage fluid","volume":"12","author":"Zou","year":"2024","journal-title":"Adv. Sci."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1946336\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:40:17Z","timestamp":1790656817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1946336\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":35,"alternative-id":["10.3389\/fcimb.2026.1946336"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1946336","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"article-number":"1946336"}}