In βENaC-overexpressing (βENaC-Tg) mice, an imbalance between Na+ absorption and Cl− secretion results in volume depletion (dehydration) of airway surfaces causing a spontaneous lung disease that shares key features with COPD in humans including impaired mucus clearance, airway mucus obstruction, goblet cell metaplasia, chronic neutrophilic inflammation with increased levels of the IL-8 homologue KC, reduced clearance of bacterial pathogens and emphysema [4], [7], [8]. Here, CALCA is linked to pulmonary emphysema.