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Pulmonary microbiome and gene expression signatures differentiate lung function in pediatric hematopoietic cell transplant candidates.
Zinter, Matt S; Versluys, A Birgitta; Lindemans, Caroline A; Mayday, Madeline Y; Reyes, Gustavo; Sunshine, Sara; Chan, Marilynn; Fiorino, Elizabeth K; Cancio, Maria; Prevaes, Sabine; Sirota, Marina; Matthay, Michael A; Kharbanda, Sandhya; Dvorak, Christopher C; Boelens, Jaap J; DeRisi, Joseph L.
Afiliação
  • Zinter MS; School of Medicine, Department of Pediatrics, Division of Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Versluys AB; School of Medicine, Department of Pediatrics, Division of Allergy, Immunology, and Bone Marrow Transplantation, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Lindemans CA; University Medical Center Utrecht, Department of Pediatric Stem Cell Transplantation, Utrecht, 3584 CX, Netherlands.
  • Mayday MY; Princess Maxima Center for Pediatric Oncology, Department of Hematopoietic Cell Transplantation, Utrecht 3584 CX, Netherlands.
  • Reyes G; University Medical Center Utrecht, Department of Pediatric Stem Cell Transplantation, Utrecht, 3584 CX, Netherlands.
  • Sunshine S; Princess Maxima Center for Pediatric Oncology, Department of Hematopoietic Cell Transplantation, Utrecht 3584 CX, Netherlands.
  • Chan M; Department of Pathology, Graduate Program in Experimental Pathology, and Yale Stem Cell Center, Yale University, New Haven, CT 06510, USA.
  • Fiorino EK; School of Medicine, Department of Pediatrics, Division of Critical Care Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Cancio M; School of Medicine, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Prevaes S; School of Medicine, Department of Pediatrics, Division of Pulmonology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Sirota M; WC Medical College, Department of Pediatrics, Division of Pulmonology, Allergy and Immunology, Cornell University, New York City, NY 10065, USA.
  • Matthay MA; WC Medical College, Department of Pediatrics, Cornell University, New York City, NY 10065, USA.
  • Kharbanda S; Department of Pediatric Stem Cell Transplantation and Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USA.
  • Dvorak CC; Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, Netherlands.
  • Boelens JJ; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
  • DeRisi JL; School of Medicine, Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Sci Transl Med ; 14(635): eabm8646, 2022 03 09.
Article em En | MEDLINE | ID: mdl-35263147
ABSTRACT
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fibrose Pulmonar / Transplante de Células-Tronco Hematopoéticas / Microbiota Tipo de estudo: Prognostic_studies Limite: Child / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fibrose Pulmonar / Transplante de Células-Tronco Hematopoéticas / Microbiota Tipo de estudo: Prognostic_studies Limite: Child / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article