Subsequent investigations utilizing normal and CF and COPD-diseased primary and immortalized human airway cells, along with studies in mice, reveal that PYO inhibits FOXA2 expression via the activation of antagonistic signaling cascades, among others, EGFR-PI3K-AKT, EGFR-MEK-ERK, and IL-13R-STAT6-SPDEF, leading to goblet cell hyperplasia and metaplasia and overexpression and hypersecretion of mucus (89, 90, 92). Here, EGFR is linked to cystic fibrosis.