Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudohypoaldosteronism

Background Active sodium absorption is the dominant mechanism of ion transp ort in airway epithelium, but its role in pulmonary physiology and airway h ost defense is unknown. To address this question, we studied the function o f airway epithelial cells and determined the frequency of pulmonary symptom s in patients with systemic pseudohypoaldosteronism, a salt-losing disorder caused by loss-of-function mutations in the genes for the epithelial sodiu m channel. Methods In nine patients 1.5 to 22 years of age who had systemic pseudohypo aldosteronism, we tested for mutations in the genes for the epithelial sodi um channel, estimated the rate of sodium transport in the airway, determine d the volume and ion composition of airway surface liquid, reviewed clinica l features, collected laboratory data pertinent to pulmonary function, and, in three adults, measured mucociliary clearance. Results The patients with systemic pseudohypoaldosteronism had loss-of-func tion mutations in the genes for the epithelial sodium-channel subunits, no sodium absorption from airway surfaces, and a volume of airway surface liqu id that was more than twice the normal value. The mean (+/-SE) mucociliary transport rate was higher in the 3 adult patients than in 12 normal subject s (2.0+/-0.7 vs. 0.5+/-0.3 percent per minute, P=0.009). Young patients (th ose five years of age or less) all had recurrent episodes of chest congesti on, coughing, and wheezing, but no airway infections with Staphylococcus au reus or Pseudomonas aeruginosa. Older patients (those more than five years of age) had less frequent respiratory symptoms. Conclusions Patients with systemic pseudohypoaldosteronism fail to absorb l iquid from airway surfaces; the result is an increased volume of liquid in the airways. These results demonstrate that sodium transport has a role in regulating the volume of liquid on airway surfaces. (N Engl J Med 1999;341: 156-62.) (C) 1999, Massachusetts Medical Society.