Upper and Lower Respiratory Tract Compartmentalization in Pediatric Stem Cell Transplantation.
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Evans Erica M, Mayday Madeline Y, Pearce Emma M, Iwanaga Kensho, Ly Ngoc P, Church Gwynne D, Reyes Gustavo, Simon Miriam R, Blum Jacob, Kim Hanna, Mu Jessica, Baez-Maidana Jazmin, Auletta Jeffrey J, Shaw Peter J, Kreml Erin M, Martin Paul L, Duncan Christine N, Rowan Courtney M, Godder Kamar, Hurley Caitlin, Cuvelier Geoffrey D E, Qayed Muna, Abdel-Azim Hisham, Keating Amy K, Fitzgerald Julie C, Hanna Rabi, Killinger James S, Hume Janet R, Quigg Troy C, Castillo Paul, Satwani Prakash, Moore Theodore B, Dvorak Christopher C, Zinter Matt S, Pediatric Transplantation And Cell Therapy Consortium
Аннотация
OBJECTIVES: To determine whether microbiome and gene expression perturbations are shared along the respiratory tract or isolated to the alveoli in pediatric HCT patients with lung injury.
METHODS: We performed bulk RNA sequencing on 206 paired nasal and BAL samples from 160 HCT patients and 17 healthy controls enrolled at 28 children's hospitals (2016-2025). Microbial and human transcripts were compared using multivariable models accounting for age, sex, and paired sampling.
MEASUREMENTS AND MAIN RESULTS: HCT BAL and nasal transcriptomes differed across 13,698 genes, 48 cellular components, and network interactions linking inflammation, reactive oxygen species, and immunometabolism. Minimal BAL-nasal correlation was observed in gene expression levels (median ρ = 0.03, IQR -0.03 to 0.08) or fractional abundance of key cells such as neutrophils and CD8 + T-cells. BAL microbiomes harbored fewer commensal bacteria and more fungi and DNA viruses. BAL bacterial RNA was associated with diminished immune signaling whereas nasal bacterial RNA aligned with inflammatory gene expression. Further, only BAL microbial RNA was linked to transcriptional shifts in epithelial injury response, keratinization, and collagen deposition. Finally, BAL commensal microbiome depletion, epithelial injury, and immune dysregulation signatures were associated with death or prolonged mechanical ventilation, whereas nasal samples provided minimal prognostic information.
CONCLUSIONS: These data support alveolar compartmentalization in pediatric HCT and emphasize the ongoing need for minimally-invasive but informative diagnostics.