Pulmonary Epithelial Sodium-Channel Dysfunction and Excess Airway Liquid in Pseudohypoaldosteronism

作者：Eitan Kerem, Tzvy Bistritzer, Aaron Hanukoglu, Thomas Hofmann, Zhaoqing Zhou, William D. Bennett, Eithne F. MacLaughlin, Pierre Barker, Martin A. Nash, Lynne M. Quittell, Richard C. Boucher, Vera Homolya, Bruce S. Keenan, Michael R. Knowles · 发表于：New England Journal of Medicine · 年份：1999 · DOI：10.1056/nejm199907153410304 · 被引用次数：356 · 研究领域：Ion Transport and Channel Regulation、Asthma and respiratory diseases、Cystic Fibrosis Research Advances

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 Pse...