We identified a series of significant pathways, including BCR signaling pathway, ECM-related pathways, NF-κB and TGF-β signaling pathways, and several hub genes (i.e. CD19, BLK, MS4A1, POU2AF1, and COL6A1) that may be involved in the emphysema phenotype of COPD. Here, BLK is linked to pulmonary emphysema.