Cystic Fibrosis and the Salt Controversy

fluid, and normal and CF ASL did not differ in fluid osmo-School of Medicine lality or in Na ϩ and Cl Ϫ concentrations. The major differ-Baltimore, Maryland 21205 ences between normal and CF epithelia were in the volume of fluid absorbed and in mucociliary clearance. Twenty-four hours after 50 ␮l of saline was placed on the cells, the depth of fluid on the normal cultures was Introduction 18 ␮m, but was only 6.0 ␮m for CF cultures. The height The human airway has two aqueous layers that are vital of the surface liquid in CF cultures was reduced to the for normal lung function. A mucous layer traps inhaled level of the outstretched cilia, dramatically impairing bacteria and foreign particles. A thin layer of airway mucus transport such that mucus accumulated in sta-surface fluid (ASL) lines the epithelial surface, providing tionary " plaque-like masses. " This effect was reversible: a microenvironment that enables cilia to clear mucus simply adding more fluid onto the surface of the cultures from the airway. Cystic fibrosis (CF) is a disease associ-restored mucus transport. These results suggest that a ated in part with impaired mucociliary clearance, abnor-major defect in CF is underhydration of the airways, mally thick mucus, chronic infections, and inflammation leading to impaired mucociliary clearance and thickened in the lung. The lungs of healthy individuals are free from mucus. bacterial infection, whereas the lungs of CF patients are The Salt Hypothesis chronically infected by bacteria such as Staphylococcus To study the susceptibility of CF airways to infection, aureus and Pseudomonas aeruginosa, which can de-Welsh and colleagues (Smith et al., 1996) inoculated P. stroy the lungs (reviewed by Rosenstein, 1998). Re-aeruginosa onto the apical surface of primary cultures cently, two groups have proposed opposing theories of human airway epithelial cells. Surprisingly, the normal regarding the role of lung hydration versus salt concen-epithelia remained viable and uninfected, whereas the tration in normal airway defense and in causing in-CF epithelia became colonized. When diluted with wa-creased bacterial infections in CF patients. The goals ter, ASL from CF epithelia killed P. aeruginosa. These of this review are to evaluate the two theories and to results suggest that a natural bactericidal factor is pres-attempt to resolve these seemingly contradictory re-ent in normal and CF ASL, but it is inactivated by high sults. Secretory Model of CF salt in CF epithelia. They then measured ASL ion compo-Cl Ϫ transport …