Small molecule inhibitor of neutrophil elastase reduces emphysema in mice with cystic fibrosis-like lung disease

Background: Increased neutrophil elastase (NE) activity in bronchoalveolar lavage (BAL) fluid in newborns with cystic fibrosis (CF) has been shown to correlate with lung damage in juvenile age. Mice with airway- specific overexpression of the epithelial Na+ channel (βENaC-Tg) phenocopy CF lung disease with mucus obstruction, chronic inflammation and emphysema. Genetic deletion of NE in βENaC-Tg mice reduced airway inflammation and emphysema, indicating that NE may serve as a therapeutic target. Aim: We used βENaC-Tg mice to assess if pharmacologic NE inhibition by Sivelestat has a therapeutic effect on emphysema…