Effective mucus clearance is essential for respiratory health.

Studies of the pathogenesis of cystic fibrosis (CF) and primary ciliary dyskinesia (PCD), as well as novel genetic mouse models, vividly illustrate that effective “mucus clearance” is a critical innate airway defense mechanism. Modern physics, physical chemistry, biochemistry, and cell and systems biology are revealing the structure of the mucus clearance apparatus and elucidating key parameters underlying its efficient function. New paradigms are evolving to describe the interaction of the near-cell surface environment with overlying mucus, the dominant role of adequate hydration for effective mucus clearance, the role of nucleotide and nucleoside signaling to regulate airway surface hydration, the physiochemical basis of mucus adhesion, and the pathophysiologic consequences of impaired mucus clearance. The recent success of hypertonic saline to restore surface hydration and improve mucus clearance in CF suggests that novel therapeutic strategies will be similarly efficacious in other airway diseases, including chronic obstructive pulmonary disease (COPD).