When viewed in combination, the observed increase in amiloride-insensitive ISC, the reduced forskolin/IBMX response, and the comparable magnitude of total chloride secretory ISC and CFTRinh-172–sensitive ISC in ETI-treated compared with ET-treated cultures suggest that chronic exposure to ivacaftor in combination with elexacaftor and tezacaftor induces constitutive activation of F508del-CFTR in CF nasal epithelial cultures grown in PneumaCult medium. Here, CFTR is linked to cystic fibrosis.