Increased Bioelectric Potential Difference across Respiratory Epithelia in Cystic Fibrosis

Abstract

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 less than 0.05). Superfusion of the luminal surface with amiloride, an inhibitor of active sodium absorption, induced greater reductions in both nasal and airway potential difference 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.

Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia

“…The level of the mRNA expression appeared to decrease distally through the airways, consistent with previous PCR data (Trapnell et al, 1991) and functional studies (Knowles et al, 1981).…”

Cystic Fibrosis F508del Patients Have Apically Localized CFTR in a Reduced Number of Airway Cells

“…Considering the substantial evidence of increased nasal potential differences in patients with CF (Alton et al, 1987;Hay and Geddes, 1985;Hofmann et al, 1997;Knowles et al, 1981), it might be expected that in patients with CF the proportion of TCE cells with F508del-CFTR in the AR (22%) would be lower. The sensitivity of the nasal potential difference assay for residual Cl Ϫ secretory activity, however, remains to be determined (Pilewski and Frizzell, 1999).…”

Salmeterol for the Prevention of High-Altitude Pulmonary Edema

“…16,17 In a double-blind, placebo-controlled study, we tested whether the prophylactic inhalation of the betaadrenergic agonist salmeterol at a dose shown to stimulate the clearance of alveolar fluid 18 decreases the incidence of pulmonary edema during exposure to high altitudes in subjects who are prone to high-altitude pulmonary edema. We also measured the nasal transepithelial potential difference (a marker of the transepithelial sodium and water transport in the distal air-ways) [19][20][21][22] at low altitude in subjects who were prone to high-altitude pulmonary edema, subjects who were resistant to this condition, and subjects who had had transient perinatal pulmonary hypertension.…”

“…The nasal transepithelial potential difference was measured with a recording bridge (polyethylene tubing filled with Ringer's solution) inserted under the inferior turbinate. 19,20 The intranasal recording bridge and a subcutaneous reference bridge (a sterile 21-gauge needle filled with agar and Ringer's solution) were linked by matched electrodes (Dri-Ref, World Precision Instruments) to a high-impedance voltmeter (Isomil, World Precision Instruments). During the measuring process, the recording bridge was perfused with isothermic (37°C) Ringer's solution (at a rate of 0.2 ml per minute).…”

“…Once a stable recording of potential difference had been obtained, amiloride (10 -4 mol per liter) was superfused at a rate of 5 ml per minute for three minutes through a second catheter. [19][20][21] …”