ACUTE AND LONG-TERM AMILORIDE INHALATION IN CYSTIC-FIBROSIS LUNG-DISEASE - A RATIONAL APPROACH TO CYSTIC-FIBROSIS THERAPY

Cystic fibrosis (CF) is the most common inherited fatal disorder among Caucasians. Bronchial mucus in CF contains more potassium and less sodium, which may be due to increased sodium absorption, resulting in a reduced airway water content. We studied 23 patients with CF after inhalation of normal saline or amiloride (10-3 M), a sodium transport blocker. Mucociliary clearance (MC) and cough clearance (CC) were determined with a gamma camera that traced the movement of 99mTc-labeled, hardened erythrocytes over a 1-h period after the patients inhaled these particles as an aerosol. Before and after each investigation pulmonary function tests (PFT) and blood pressure (BP) were measured. Sputum thread formation was measured by means of a filancemeter. Six of the patients also completed a 3-wk trial of amiloride inhalation therapy. MC increased significantly (p < 0.001) after acute amiloride inhalation (bronchial deposition, 0.07 mg amiloride) compared with that in the saline control. CC also increased, but not as much as MC. After 3 wk of amiloride inhalation (2 times a day) clearance values (both MC and CC) were markedly enhanced (p < 0.01); after a similar period of saline inhalation, clearance values were not different from baseline. Sputum filance values also decreased significantly after amiloride inhalation. There were no adverse effects of the amiloride inhalation compared with saline. We conclude that amiloride inhalation administered as a single doses or as long-term therapy is able to increase MC and CC in CF airways and that the effect of 10-3 M amiloride inhalation on MC lasts at least 40 min. These results indicate that further clinical studies of long-term amiloride inhalation in patients with CF should be undertaken. This is the first line of evidence that an inhaled diuretic drug such as amiloride is able to enhance mucus clearance favorably in patients with CF. The mechanism is most likely due to the alteration of water content within the airways.