EFFECT OF URIDINE 5'-TRIPHOSPHATE PLUS AMILORIDE ON MUCOCILIARY CLEARANCE IN ADULT CYSTIC-FIBROSIS

Cystic fibrosis (CF) is characterized by abnormal airway epithelial el ectrolyte transport leading to viscous airway secretions that are diff icult to clear. By enhancing Cl- secretion onto and blocking Na+ absor ption from the airway surface, treatment with aerosolized uridine 5'-t riphophate (UTP) plus amiloride may improve the rheology of airway sec retions and enhance mucociliary clearance in patients with CF. After p erforming safety studies of aerosolized UTP/amiloride in adult patient s with CF, we investigated the effects of inhaled vehicle and UTP/amil oride on mucociliary clearance of [Tc-99m] iron oxide particles from t he airways of adult patients with CF (n = 14). We found no clinically significant adverse effects from inhalation of therapeutic doses of UT P/amiloride. Mean baseline peripheral clearance rates during the first 40 min of clearance measurements were significantly less in patients with CF than in normal subjects (mean +/- SE: 0.30 +/- 0.05 versus 0.5 4 +/- 0.07%/min, respectively; p = 0.01). Aerosolized UTP and amilorid e in combination improved mucociliary clearance from the peripheral ai rways of the CF lungs to near normal values (0.51 +/- 0.09%/min; p = 0 .04) during this period. These data support the concept for the use of UTP in combination with amiloride as therapy to improve clearance of secretions from the lungs of patients with CF.