Consistent with a higher expression of Scnn1b (βENaC) gene in lung tissue of C57/BL6J-βENaC-Tg mice (Fig. 1b), typical COPD/CF-like phenotypes were clearly observed in C57/BL6J-βENaC-Tg mice, such as the presence of mucus plug and obstruction (Fig. 1c–g), increased expression of Muc5ac and fucose levels in bronchoalveolar lavage fluid (BALF) (Fig. 1h,i), gob5 gene induction in lung tissue (Fig. 1j) and immune cells-associated pulmonary inflammation (Fig. 1k,l). Here, SCNN1B is linked to chronic obstructive pulmonary disease.