Increased Bioelectric Potential Difference across Respiratory Epithelia in Cystic Fibrosis

To investigate respiratory epithelial function in cystic fibrosis, we measured the transepithelial electrical potential difference across the upper and lower respiratory mucosa in patients with cystic fibrosis and control subjects. The nasal potential difference in the 24 patients with cystic fibrosis exceeded by more than 3 standard deviations the mean voltage in healthy controls, subjects with other diseases, and subjects heterozygous for cystic fibrosis. Potential differences in lower airways were measured in four patients and were significantly greater than in controls (P<0.05). Superfusion of the luminal surface with amiloride, an inhibitor of active sodium absorption, induced greater reductions in both nasal and airway potential differences in patients than in controls. We conclude that the increased respiratory-epithelial potential differences appear to be a specific abnormality in homozygotes for cystic fibrosis. The greater reduction in potential difference in response to amiloride suggests that absorption of excess salt and perhaps liquid from respiratory epithelial surfaces contributes to the pathogenesis of lung disease in cystic fibrosis. (N Engl J Med. 1981; 305:148995.). Abnormalities in the electrolyte and water content of luminal liquid or “secretions” of the airways, sweat glands, intestinal and reproductive tracts, and pancreas suggest that cystic fibrosis is characterized by a generalized epithelial dysfunction. Airway secretions are tenacious and excessively thick. Although a search for the cause of this abnormal surface liquid has failed to identify unique mucus glycoproteins, altered electrolyte composition and lower water content (“dehydration“) of airway secretions from patients with cystic fibrosis have been reported