Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudohypoaldosteronism.
BACKGROUND
Active sodium absorption is the dominant mechanism of ion transport in airway epithelium, but its role in pulmonary physiology and airway host defense is unknown. To address this question, we studied the function of airway epithelial cells and determined the frequency of pulmonary symptoms in patients with systemic pseudohypoaldosteronism, a salt-losing disorder caused by loss-of-function mutations in the genes for the epithelial sodium channel.


METHODS
In nine patients 1.5 to 22 years of age who had systemic pseudohypoaldosteronism, we tested for mutations in the genes for the epithelial sodium channel, estimated the rate of sodium transport in the airway, determined the volume and ion composition of airway surface liquid, reviewed clinical features, collected laboratory data pertinent to pulmonary function, and, in three adults, measured mucociliary clearance.


RESULTS
The patients with systemic pseudohypoaldosteronism had loss-of-function mutations in the genes for the epithelial sodium-channel subunits, no sodium absorption from airway surfaces, and a volume of airway surface liquid 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 subjects (2.0+/-0.7 vs. 0.5+/-0.3 percent per minute, P=0.009). Young patients (those five years of age or less) all had recurrent episodes of chest congestion, coughing, and wheezing, but no airway infections with Staphylococcus aureus 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 liquid 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.
Pediatric Respiratory Medicine and Cystic Fibrosis Center, Shaare Zedek Medical Center, Hebrew University Medical School, Jerusalem, Israel.
E
E
Kerem
T
T
Bistritzer
A
A
Hanukoglu
T
T
Hofmann
Z
Z
Zhou
W
W
Bennett
E
E
MacLaughlin
P
P
Barker
M
M
Nash
L
L
Quittell
R
R
Boucher
M R
MR
Knowles
D000042:Absorption; D000293:Adolescent; D000328:Adult; D001826:Body Fluids / Q000378:metabolism*; D001999:Bronchoscopy; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D017136:Ion Transport; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D011546:Pseudohypoaldosteronism / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
D015222:Sodium Channels; D012964:Sodium