دورية أكاديمية
أعرض في EDS

Pulmonary microbiome and gene expression signatures differentiate lung function in pediatric hematopoietic cell transplant candidates.

التفاصيل البيبلوغرافية
العنوان: Pulmonary microbiome and gene expression signatures differentiate lung function in pediatric hematopoietic cell transplant candidates.
المؤلفون: Zinter MS; School of Medicine, Department of Pediatrics, Division of Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.; School of Medicine, Department of Pediatrics, Division of Allergy, Immunology, and Bone Marrow Transplantation, University of California, San Francisco, San Francisco, CA 94143, USA., Versluys AB; University Medical Center Utrecht, Department of Pediatric Stem Cell Transplantation, Utrecht, 3584 CX, Netherlands.; Princess Maxima Center for Pediatric Oncology, Department of Hematopoietic Cell Transplantation, Utrecht 3584 CX, Netherlands., Lindemans CA; University Medical Center Utrecht, Department of Pediatric Stem Cell Transplantation, Utrecht, 3584 CX, Netherlands.; Princess Maxima Center for Pediatric Oncology, Department of Hematopoietic Cell Transplantation, Utrecht 3584 CX, Netherlands., Mayday MY; Department of Pathology, Graduate Program in Experimental Pathology, and Yale Stem Cell Center, Yale University, New Haven, CT 06510, USA., Reyes G; School of Medicine, Department of Pediatrics, Division of Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USA., Sunshine S; School of Medicine, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA., Chan M; School of Medicine, Department of Pediatrics, Division of Pulmonology, University of California, San Francisco, San Francisco, CA 94143, USA., Fiorino EK; WC Medical College, Department of Pediatrics, Division of Pulmonology, Allergy and Immunology, Cornell University, New York City, NY 10065, USA., Cancio M; WC Medical College, Department of Pediatrics, Cornell University, New York City, NY 10065, USA.; Department of Pediatric Stem Cell Transplantation and Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USA., Prevaes S; Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, Netherlands., Sirota M; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA 94143, USA.; School of Medicine, Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA., Matthay MA; School of Medicine, Cardiovascular Research Institute, Departments of Medicine and Anesthesiology, University of California, San Francisco, San Francisco, CA 94143, USA., Kharbanda S; School of Medicine, Department of Pediatrics, Division of Allergy, Immunology, and Bone Marrow Transplantation, University of California, San Francisco, San Francisco, CA 94143, USA., Dvorak CC; School of Medicine, Department of Pediatrics, Division of Allergy, Immunology, and Bone Marrow Transplantation, University of California, San Francisco, San Francisco, CA 94143, USA., Boelens JJ; WC Medical College, Department of Pediatrics, Cornell University, New York City, NY 10065, USA.; Department of Pediatric Stem Cell Transplantation and Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USA., DeRisi JL; School of Medicine, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
المصدر: Science translational medicine [Sci Transl Med] 2022 Mar 09; Vol. 14 (635), pp. eabm8646. Date of Electronic Publication: 2022 Mar 09.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Association for the Advancement of Science
مواضيع طبية MeSH: Hematopoietic Stem Cell Transplantation* , Microbiota*/genetics , Pulmonary Fibrosis*, Child ; Humans ; Lung/metabolism ; Transcriptome/genetics
مستخلص: Impaired baseline lung function is associated with mortality after pediatric allogeneic hematopoietic cell transplantation (HCT), yet limited knowledge of the molecular pathways that characterize pretransplant lung function has hindered the development of lung-targeted interventions. In this study, we quantified the association between bronchoalveolar lavage (BAL) metatranscriptomes and paired pulmonary function tests performed a median of 1 to 2 weeks before allogeneic HCT in 104 children in The Netherlands. Abnormal pulmonary function was recorded in more than half the cohort, consisted most commonly of restriction and impaired diffusion, and was associated with both all-cause and lung injury-related mortality after HCT. Depletion of commensal supraglottic taxa, such as Haemophilus , and enrichment of nasal and skin taxa, such as Staphylococcus , in the BAL microbiome were associated with worse measures of lung capacity and gas diffusion. In addition, BAL gene expression signatures of alveolar epithelial activation, epithelial-mesenchymal transition, and down-regulated immunity were associated with impaired lung capacity and diffusion, suggesting a postinjury profibrotic response. Detection of microbial depletion and abnormal epithelial gene expression in BAL enhanced the prognostic utility of pre-HCT pulmonary function tests for the outcome of post-HCT mortality. These findings suggest a potentially actionable connection between microbiome depletion, alveolar injury, and pulmonary fibrosis in the pathogenesis of pre-HCT lung dysfunction.
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معلومات مُعتمدة: T32 AI060537 United States AI NIAID NIH HHS; R35 HL140026 United States HL NHLBI NIH HHS; K23 HL146936 United States HL NHLBI NIH HHS; R01 HL134828 United States HL NHLBI NIH HHS; F31 AI150007 United States AI NIAID NIH HHS; United States HHMI Howard Hughes Medical Institute; K12 HD000850 United States HD NICHD NIH HHS; L40 HL138866 United States HL NHLBI NIH HHS
تواريخ الأحداث: Date Created: 20220309 Date Completed: 20220426 Latest Revision: 20230313
رمز التحديث: 20230313
مُعرف محوري في PubMed: PMC9487170
DOI: 10.1126/scitranslmed.abm8646
PMID: 35263147
قاعدة البيانات: MEDLINE
الوصف
تدمد:1946-6242
DOI:10.1126/scitranslmed.abm8646