This emphasizes that further investigation of ABCC4 and PDE-4 inhibitors as a potential add-on combinatorial therapy should be performed in primary human airway epithelial cells from a large subset of CF subjects, covering a wide-range of CFTR variants with compromised CFTR expression or function, in order to determine which patient populations could benefit from cAMP modulation therapy. This evidence concerns the gene PDE4A and cystic fibrosis.