The dual phosphodiesterase 3 and 4 inhibitor RPL554 (ensifentrine), in clinical development for chronic obstructive pulmonary disease (COPD) and asthma [76], was shown to activate CFTR with rare class III and IV mutations [77,78] and was tested in a small phase II trial with promising results ([79] & NCT02919995). Here, CFTR is linked to chronic obstructive pulmonary disease.