Inflammation and apoptosis are deregulated in sputum cells derived from patients with post-infectious bronchiolitis obliterans

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Post-infectious bronchiolitis obliterans (PiBO) is a chronic lung disease that occurs after respiratory infections and leads to persistent inflammation and fibrotic changes in the small airways. Using gene expression analysis, the aim of the present study was to identify differentially expressed genes (DEGs) in sputum cells derived from patients with PiBO. Clinical history, lung function parameters, and induced sputum samples for gene expression analysis and sputum cell counts were collected from patients with PiBO (n=9) and healthy controls (n=8). Sequencing of mRNA was performed by MACE-Seq and evaluation of the biological targets was done by KEGG pathway enrichment analysis. Patients with PiBO had significantly lower lung function values and sputum-neutrophil counts were significantly increased among patients compared with controls. MACE analysis revealed a total of 542 DEGs passed significance threshold for padj. <0.05 (FC >2). KEGG pathway analysis showed that DEGs were mainly enriched in NF-kappa B signalling (fdr=1.05 e-09, 20 genes) and TNF signalling (fdr=1.15e-07, 18 genes). Nine corresponding mRNAs were identified that are involved in both pathways. Among them, the expression of TRAF1, CFLAR, RELA, BIRC3 and TNFAIP3 correlated significantly with lung function impairment. Interestingly, these mRNAs are also implicated in the process of apoptosis. Our results demonstrate an aberrant mRNA expression profile in PiBO which impacts pathways responsible for the regulation of inflammation and apoptosis. Understanding this interaction provides important insights into the progression and persistence of PiBO providing potential future therapeutic options.

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