Upper and Lower Respiratory Tract Compartmentalization in Pediatric Stem Cell Transplantation

Area of Science:

• Pulmonary Medicine
• Immunology
• Microbiology

Background:

• Lung injury is a significant complication following hematopoietic stem cell transplantation (HCT), driven by infection, chemotherapy, and inflammation.
• Current diagnostic approaches analyzing bronchoalveolar lavage (BAL) fluid are invasive, necessitating the development of minimally-invasive alternatives.

Purpose of the Study:

• To investigate whether microbiome and gene expression alterations in pediatric HCT patients with lung injury are localized to the alveoli or present throughout the respiratory tract.
• To compare the diagnostic and prognostic utility of nasal versus BAL samples.

Main Methods:

• Bulk RNA sequencing was performed on paired nasal and BAL samples from 160 pediatric HCT patients and 17 healthy controls.
• Microbial and human transcripts were analyzed using multivariable models, accounting for clinical covariates.
• Gene expression and microbiome data were compared between nasal and BAL compartments.

Main Results:

• Significant differences in gene expression and cellular components were observed between HCT BAL and nasal samples, with minimal correlation in gene expression levels or immune cell abundance.
• BAL microbiomes showed distinct profiles, with fewer commensal bacteria and increased fungi/DNA viruses compared to nasal samples.
• BAL microbial RNA was associated with epithelial injury and collagen deposition, while nasal microbial RNA correlated with inflammation; BAL findings were linked to poor outcomes, unlike nasal samples.

Conclusions:

• The findings indicate compartmentalization of pathobiologic processes within the alveoli in pediatric HCT-associated lung injury.
• These results underscore the need for informative, minimally-invasive diagnostic tools tailored to the alveolar compartment.