Integrating Pulmonary and Systemic Transcriptomic Profiles to Characterize Lung Injury after Pediatric Hematopoietic...

Area of Science:

• Hematology
• Pulmonology
• Genomics

Background:

• Hematopoietic stem cell transplantation (HCT) can cause lung injury.
• Bronchoalveolar lavage (BAL) is invasive and difficult for serial monitoring.
• Peripheral blood as a surrogate for lung sampling in HCT patients is unproven.

Purpose of the Study:

• To determine if peripheral blood transcriptomes can serve as a minimally-invasive surrogate for pulmonary sampling in pediatric HCT patients.
• To compare BAL and peripheral blood transcriptomes for insights into post-HCT lung injury.

Main Methods:

• Compared 210 paired BAL and peripheral blood transcriptomes from 166 pediatric HCT patients.
• Analyzed gene expression, gene sets, cell fractions, and T-/B-cell receptor clonotypes.
• Integrated paired transcriptomes to identify patient subgroups and survival associations.

Main Results:

• Minimal correlation found between BAL and blood mRNA abundance for individual genes, gene sets, or cell fractions.
• Distinct transcriptional programs identified: BAL showed immune, epithelial-mesenchymal transition, and hypoxia pathways; blood showed endothelial injury, DNA repair, and metabolism pathways.
• Paired transcriptome integration identified patient groups with differential hypoxia rates and outcomes, with one group showing significantly worse outcomes.

Conclusions:

• BAL and peripheral blood transcriptomes provide distinct, compartmentalized insights into lung injury mechanisms post-HCT.
• Peripheral blood cannot fully replace BAL for pulmonary assessment but offers complementary systemic information.
• Transcriptional profiling of both compartments aids in understanding and potentially managing post-HCT lung injury.