['Acquired CFTR dysfunction may contribute to COPD pathogenesis and is a potential therapeutic target.', 'To determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis; and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770).', 'Primary human bronchial epithelial cells (HBE) and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation; acrolein modifications on CFTR protein were determined by mass spectroscopic analysis of purified protein; and the functional microanatomy of the airway epithelia was measured by one-micrometer resolution optical coherence tomography (μOCT).', 'CSE reduced CFTR-dependent current in HBE (P<0.05) and human bronchi (P<0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open channel probability by ~75% immediately after exposure (P<0.05), whereas surface CFTR expression was partially reduced with chronic exposure but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P<0.05) and ciliary beat frequency (P<0.05) within 60 minutes that was restored by co-administration with ivacaftor (P<0.005).'] Does the CFTR Potentiator Ivacaftor augment Mucociliary Clearance Abrogating CFTR Inhibition by Cigarette Smoke?