1. Combination Therapy with Cystic Fibrosis Transmembrane Conductance Regulator Modulators Augment the Airway Functional Microanatomy

    Combination Therapy with Cystic Fibrosis Transmembrane Conductance Regulator Modulators Augment the Airway Functional Microanatomy

    Recently approved therapies that modulate CFTR function have shown significant clinical benefit, but recent investigations regarding their molecular mechanism when used in combination have not been consistent with clinical results. We employed Micro-Optical Coherence Tomography (µOCT) as a novel means to assess the mechanism of action of CFTR modulators, focusing on the effects on mucociliary clearance. Primary human airway monolayers from patients with a G551D mutation responded to ivacaftor treatment with increased ion transport, airway surface liquid depth, ciliary beat frequency, and mucociliary transport rate, in addition to decreased effective viscosity of the mucus layer, a unique mechanism established by ...

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