Different Transcriptome Features of Peripheral Blood Mononuclear Cells in Non-Emphysematous Chronic Obstructive Pulmonary Disease [COPD_PBMC]
Non-emphysematous COPD, which is defined based on chest computed tomography (CT) findings, may present different transcriptome features of peripheral blood mononuclear cells (PBMCs) derived from bone marrow (BM). In obstructive disorder-fixed COPD, including the airway-dominant phenotype, the upregulated differentially expressed genes (DEGs) were mainly related to Th2 inflammation, suppression of pulmonary vascular remodeling, and the function of BM-derived progenitor cells. Airway-dominant phenotypes are associated with less obstructive impairment. The upregulated DEGs in emphysematous COPD could be associated with airway inflammation and remodeling, suggesting an asthmatic component. Upregulated XCL1, PRKCZ, TMEM102, CD200R1, and AQP1 levels are associated with the activation of T lymphocytes and eosinophils. The upregulation of keratan sulfate biosynthesis and metabolic processes is associated with protection against destruction of the distal airways. The upregulation of ITGA3 could augment interactions with extracellular matrix proteins. COL6A1 may augment the profibrotic mast cell phenotype during the deposition of alveolar collagen VI. The upregulated HSPG2, PDGFRB and PAK4 may contribute to airway wall thickening. The upregulated SERPINF1 could explain the better preserved vascular bed, and the upregulation of SERPINF1 and ISM1 seem to protect against emphysema formation. These patterns in PBMCs may be related to the pathogenesis of nonemphysematous COPD. Overall design: To investigate the pathogenesis of COPD in PBMCs, we compared COPD (n=26) and healthy controls (n=13) samples by RNA-seq. Then, to investigate the pathogenesis of non-emphysematous COPD, we compared samples between non-emphysematous COPD (n=14) and emphysematous COPD (n=8), respectively, by RNA-seq.