Effect of aerosolized uridine 5 '-triphosphate on mucociliary clearance inmild chronic bronchitis

Previous studies show that uridine 5 ' -triphosphate (UTP), a P2Y(2) recept or agonist, is effective at acutely enhancing mucociliary clearance in heal thy, nonsmoking adults. UTP solution for inhalation is being developed by I nspire Pharmaceuticals under the compound number INS316. In a double-blind, randomized, crossover, placebo-controlled study we tested the single-dose effect of UTP in chronic smokers with mild chronic bronchitis (n = 15) by m easuring the clearance of Tc-99m-Fe2O3 particles (4.0 mum mass median aerod ynamic diameter [MMAD]) after inhalation of nebulized placebo (0.9% saline) and two doses of UTP (20 and 100 mg in the nebulizer). On each study day, gamma camera scanning was performed over a 2-h period. After an initial dep osition scan, subjects inhaled placebo or UTP during the first 20 min of sc anning. Analysis of whole lung clearance showed that the retention-time cur ves for each day were biphasic and that the earliest break point in the ave rage curves occurred at 50 min. Mean particle clearance rate (CIr in %/min) through 50 min for placebo treatment was Cir = 0.65 +/- 0.27 whereas treat ment with UTP showed CIr significantly increased to 0.95 +/- 0.48 and 0.93 +/- 0.44 for the 20-mg and 100-mg dose respectively, p < 0.005 for both as compared with placebo. These data show that mucociliary clearance associate d with mild chronic bronchitis is acutely improved with minimal doses of ae rosolized UTP, presumably because of its stimulation of ciliary beating and hydration of airway secretions.