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Previous Volume 341:156-162 July 15, 1999 Number 3 Next

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ABSTRACT

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.

Source Information

From the Pediatric Respiratory Medicine and Cystic Fibrosis Center, Shaare Zedek Medical Center, Hebrew University Medical School, Jerusalem, Israel (E.K.); the Department of Pediatrics, Assaf Harofeh Medical Center, Zerifin, Israel (T.B.); the Department of Pediatrics, Wolfson Medical Center, Holon, Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel (A.H.); Justus Liebig Universität Kinderklinik, Pädiatrische Pneumonologie, Giessen, Germany (T.H.); the Cystic Fibrosis–Pulmonary Research and Treatment Center (Z.Z., P.B., R.B., M.R.K.) and the Center for Environmental Medicine (W.B.), University of North Carolina at Chapel Hill; the Division of Pediatric Pulmonology, Childrens Hospital Los Angeles and the University of Southern California, Los Angeles (E.M.); and the Pediatric Nephrology Division (M.N.) and Pediatric Pulmonary Division (L.Q.), Columbia–Presbyterian Medical Center, New York. Other authors were Vera Homolya, M.S. (University of North Carolina, Chapel Hill), and Bruce Keenan, M.D. (Department of Pediatrics, University of Texas, Galveston).

Address reprint requests to Dr. Knowles at the Cystic Fibrosis–Pulmonary Research and Treatment Center, 7011 Thurston-Bowles Bldg., CB 7248, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248, or at knowles{at}med.unc.edu.

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