Therefore, the major aims of this study are i) to determine HE4 level in the supernatants of cystic fibrosis bronchial epithelial (CFBE) 410− cells expressing F508del-CFTR or wt-CFTR after in vitro administration of clinically relevant concentrations of CFTR modulators as well as CFTR activators and inhibitor; ii) to analyze HE4 concentrations in plasma samples drawn from CF subjects receiving Orkambi®; and iii) to investigate the role of NF-κB pathway in HE4 expression in association with impaired CFTR function and pro-inflammatory signaling in CF. This evidence concerns the gene WFDC2 and cystic fibrosis.