TNF and chronic obstructive pulmonary disease: Neutrophils play a key role in goblet cell stimulation and mucus hyperproduction in COPD via numerous mechanisms: (i) secretion of tumor necrosis factor (TNF)-α, which induces EGFR expression in airway epithelial cells; (ii) release of reactive oxygen species (ROS), which activate EGFR; (iii) activated NE cleaves the EGFR proligand, pro-transforming growth factor (TGF)-α, releasing TGF-α, which activates EGFR in a ligand-dependent fashion; and (iv) NE causes potent goblet cell degranulation [122].