Here, we demonstrated that sustained activation of the NF-κB pathway in airway epithelium causes chronic airway inflammation with increased infiltration of lungs with macrophages, lymphocytes, and neutrophils, along with fibrotic thickening of small airway walls and profound emphysema, strongly supporting a role for NF-κB signaling in COPD. Here, NFKB1 is linked to pulmonary emphysema.