TABLE 1.

Overview of clinical trials assessing cystic fibrosis transmembrane conductance regulator (CFTR) modulators in non-cystic fibrosis lung disease

Study name/NCT	Author [ref.]	Population	Drug	Results	Sponsor
Cystic fibrosis transmembrane conductance regulator activation by roflumilast contributes to therapeutic benefit in chronic bronchitis	Lambert [114]	In vitro: HBE, smoke exposed cells	Roflumilast and Ivacaftor	Roflumilast restores CFTR activity, ASL recovery and height post smoke exposure in vitro. Effect was additive with ivacaftor.
Roflumilast combined with adenosine increases mucosal hydration in human airway epithelial cultures after cigarette smoke exposure	Tyrrell [116]	In vitro: HBE, smoke exposed cells	Roflumilast	Roflumilast improved cellular cAMP and ASL height recovery post smoke exposure.
A pharmacologic approach to acquired cystic fibrosis transmembrane conductance regulator dysfunction in smoking related lung disease.	Sloane [31]	In vitro: HBE In vivo: Smokers with and without COPD	Ivacaftor	Ivacaftor activated CFTR transport, reduced smoked induced impairment in vitro.
The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke.	Raju [65]	In vitro: smoke exposed cells	Ivacaftor	Ivacaftor partially restores ASL and CBF induced by cigarette smoke exposure.
Pilot evaluation of ivacaftor for chronic bronchitis	Solomon [120]	Chronic bronchitis: pilot study	Ivacaftor	Trend towards improved symptoms and sweat chloride.
Topic Trial NCT02135432	Rowe [121]	COPD	Ivacaftor	Results pending
A randomized, placebo controlled 4-week study in COPD of QBW251, a potentiator of the CFTR protein	Rowe [56]	COPD	QWB251	No improvement in lung clearance index. Improved sweat chloride, spirometry, inflammation, and sputum colonisation (figure 1).	Novartis
Clearing Lungs with ENaC Inhibition in PCD NCT02343445	In progress	PCD	Ivacaftor±ENaC inhibitor (VX-371)	In progress	Vertex

HBE: human bronchial epithelium; ASL: airway surface liquid interface; CBF: ciliary beat frequency; ENaC: epithelial sodium channel; PCD: primary ciliary dyskinesia.