Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease

Cell. 1998 Dec 23;95(7):1005-15. doi: 10.1016/s0092-8674(00)81724-9.


The pathogenesis of cystic fibrosis (CF) airways infection is unknown. Two hypotheses, "hypotonic [low salt]/defensin" and "isotonic volume transport/mucus clearance," attempt to link defects in cystic fibrosis transmembrane conductance regulator-mediated ion transport to CF airways disease. We tested these hypotheses with planar and cylindrical culture models and found no evidence that the liquids lining airway surfaces were hypotonic or that salt concentrations differed between CF and normal cultures. In contrast, CF airway epithelia exhibited abnormally high rates of airway surface liquid absorption, which depleted the periciliary liquid layer and abolished mucus transport. The failure to clear thickened mucus from airway surfaces likely initiates CF airways infection. These data indicate that therapy for CF lung disease should not be directed at modulation of ionic composition, but rather at restoring volume (salt and water) on airway surfaces.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Absorption
  • Animals
  • Bacterial Infections / etiology
  • Bacterial Infections / physiopathology
  • Body Water / physiology*
  • Bronchi / physiopathology*
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods
  • Cells, Cultured
  • Cilia / physiology
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / physiopathology*
  • Cystic Fibrosis / therapy
  • Dogs
  • Epithelium / physiopathology
  • Humans
  • Humidity
  • Hypertonic Solutions
  • Hypotonic Solutions
  • Isotonic Solutions / therapeutic use
  • Models, Biological
  • Mucociliary Clearance / physiology*
  • Mucus / metabolism
  • Osmolar Concentration
  • Salts / metabolism
  • Surface Tension


  • Hypertonic Solutions
  • Hypotonic Solutions
  • Isotonic Solutions
  • Salts