Building upon these findings, we tested 2 hypotheses: first, delivering recombinant human CC16 (rhCC16) protein to the lung limits the progression of CS-induced COPD-like parenchymal and airway disease in CS-exposed WT and Cc16–/– mice, and second, delivering a small molecule NF-κB inhibitor to Cc16–/– mice reduces their exuberant pulmonary inflammatory response to CS, thereby mechanistically linking the increased NF-κB activation observed in their lungs to their pulmonary phenotype when exposed to CS. The gene discussed is SCGB1A1; the disease is chronic obstructive pulmonary disease.