Transcriptome profiling of induced sputum identified up-regulated TNF-α/NF-κB signaling and down-regulated mitochondrial respiratory chain function in post-infectious Bronchiolitis obliterans

Post-infectious bronchiolitis obliterans (PiBO) is a chronic lung disease that occurs after severe lower respiratory infections and leads to persistent inflammation and fibrotic changes in the small airways. In the present study, gene expression analysis was used to identify differentially expressed genes (DEGs) in sputum cells derived from PiBO patients compared to healthy controls. Clinical history, lung function parameters, and induced sputum samples were collected from nine patients with PiBO and eight healthy controls. Multiplex immunohistochemistry (mIHC) as well as mRNA sequencing (MACE-Seq) were performed. Evaluation of the biological targets was done by KEGG pathway enrichment analysis. PiBO patients showed significantly reduced lung function parameters, an increased neutrophil count, and an altered macrophage profile in sputum. Transcriptome analysis revealed significant upregulation of the TNFα-dependent NFκB signalling pathway, as well as significant downregulation of the oxidative phosphorylation (OXPHOS). Linear regression analyses and mIHC showed a shift in macrophage polarization that appears to be responsible for the dysregulated gene expression. Notably, expression of these DEGs significantly correlated with FEV₁ lung function. These findings indicate a central role of macrophages in the immunopathology of PiBO and contribute to our understanding of the molecular mechanism involved in the disease process.