Primary ciliary dyskinesia (PCD) is a
genetic disease characterized by abnormal ciliary structure and function and impaired mucociliary clearance. Because patients with PCD use
cough clearance as an airway defense mechanism, we tested the hypothesis that aerosolized uridine-5'-triphosphate (
UTP) would improve clearance during
cough by its actions to stimulate Cl- secretion and
mucin release by goblet cells. We measured clearance during
cough in 12 patients with PCD (ages 14 to 71 yr, FEV1 43% to 89% predicted) in a double blind, randomized, crossover study after aerosolization of a single dose of
UTP (5 mg/ml, 3.5 ml) or vehicle (0.12% saline, 3.5 ml). Clearance during
cough (whole lung) was quantified during and after a series of controlled
coughs by measuring the clearance of [99mTc]Fe2O3 particles via
gamma camera scanning over 120 min. Safety parameters were recorded during and after
drug delivery. Aerosolized
UTP improved whole-lung clearance during
cough as compared with vehicle (from 0 to 60 min: 0.40 +/- 0.07%/min [
UTP] versus 0.26 +/- 0. 04%/min [vehicle] [mean +/- SEM], p = 0.01), and from 0 to 120 min: 0.38 +/- 0.05%/min [
UTP] versus 0.25 +/- 0.04%/ min [vehicle], p = 0. 02). Aerosolized
UTP is safe, with no serious adverse effects. Whole-lung clearance during
cough in patients with defective ciliary function is enhanced after inhalation of
UTP.