As hypoxic epithelial cell necrosis in mucus-obstructed airways has been identified as a strong trigger of sterile inflammation via triggering the pro-inflammatory IL-1 signaling pathway in the absence of bacterial infection in Scnn1b-Tg mice, and patients with muco-obstructive lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease [16,40,41,42], this mechanism may also contribute to the more severe inflammatory phenotype caused by the congenital deletion of Nedd4-2 in the neonatal lung. This evidence concerns the gene SCNN1B and cystic fibrosis.