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Published on: May 19, 2023
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Upper and Lower Respiratory Tract Compartmentalization in Pediatric Stem Cell Transplantation
Erica M Evans1, Madeline Y Mayday1,2, Emma M Pearce1
1Division of Critical Care Medicine, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Medrxiv : the Preprint Server for Health Sciences
|November 24, 2025
Summary
Lung injury after pediatric hematopoietic stem cell transplantation (HCT) is compartmentalized to the alveoli, not shared with the nasal tract. This highlights the need for targeted diagnostics to improve patient outcomes.
Area of Science:
- Pulmonary Medicine
- Immunology
- Microbiology
Background:
- Lung injury post-hematopoietic stem cell transplantation (HCT) arises from infection, chemotherapy, and inflammation.
- Bronchoalveolar lavage (BAL) fluid analysis reveals key signatures, but less invasive diagnostic methods are needed.
Purpose of the Study:
- To investigate if microbiome and gene expression changes in pediatric HCT patients with lung injury are shared across the respiratory tract or confined to the alveoli.
Main Methods:
- Bulk RNA sequencing was performed on 189 paired nasal and BAL samples from 160 pediatric HCT patients.
- Microbial and human transcripts were analyzed using multivariable models, controlling for clinical factors.
Main Results:
- Significant differences were found in BAL and nasal transcriptomes, with minimal correlation in gene expression and cell abundance between the two sites.
- BAL microbiomes showed distinct profiles, with fewer commensal bacteria and more fungi/viruses compared to nasal samples.
- BAL microbial RNA correlated with epithelial injury and collagen deposition, and BAL microbiome depletion predicted poor outcomes, unlike nasal samples.
Conclusions:
- These findings support the concept of alveolar compartmentalization in pediatric HCT-related lung injury.
- The study underscores the critical need for developing minimally-invasive yet informative diagnostic tools for this patient population.
