Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
23 May 2024
23 May 2024
Historique:
received:
29
11
2023
accepted:
12
04
2024
medline:
24
5
2024
pubmed:
24
5
2024
entrez:
23
5
2024
Statut:
aheadofprint
Résumé
Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies. Here we used 278 bronchoalveolar lavage (BAL) fluid samples to study the lung microenvironment in 229 pediatric patients who have undergone HCT treated at 32 children's hospitals between 2014 and 2022. By leveraging paired microbiome and human gene expression data, we identified high-risk BAL compositions associated with in-hospital mortality (P = 0.007). Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation and profound commensal depletion with viral and staphylococcal enrichment, lymphocytic activation and cellular injury, and were replicated in an independent cohort from the Netherlands (P = 0.022). In addition, a broad array of previously occult pathogens was identified, as well as a strong link between antibiotic exposure, commensal bacterial depletion and enrichment of viruses and fungi. Together these lung-immune system-microorganism interactions clarify the important drivers of fatal lung injury in pediatric patients who have undergone HCT. Further investigation is needed to determine how personalized interpretation of heterogeneous pulmonary microenvironments may be used to improve pediatric HCT outcomes.
Identifiants
pubmed: 38783139
doi: 10.1038/s41591-024-02999-4
pii: 10.1038/s41591-024-02999-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ID : K12HD000850
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : K23HL146936
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : UG1HL069254
Organisme : American Thoracic Society (American Thoracic Society, Inc.)
ID : Foundation grant
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : F31CA271571
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : P30CA008748
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : P30CA040214
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R37CA244775
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : U2CCA271890
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : P30CA008748
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : R21GM147800
Informations de copyright
© 2024. The Author(s).
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