Uridine 5′-triphosphate (UTP) is a naturally occurring agonist for P2Y2 receptors on the apical surface of ciliated respiratory epithelium. UTP stimulates salt and water transport and cilia beat frequency in human airway epithelium in vitro. Single, inhaled doses of UTP stimulate mucociliary clearance in conscious, intubated sheep and in patients with mild chronic bronchitis (smokers and former smokers), suggesting that UTP may be useful for obtaining deep-lung sputum specimens suitable for diagnostic purposes.
Study objective: UTP is being developed for the cytologic diagnosis of lung cancer under the compound number INS316 Solution for Inhalation (Inspire Pharmaceuticals; Durham, NC). Its ability to improve the quality of expectorated sputum was tested in the current study.
Design: Placebo-controlled, double-blind, escalating two-period cross-over study.
Setting: Outpatient volunteers.
Patients or participants: Twenty-six patients with mild chronic bronchitis.
Intervention: Patients attempted to expectorate a specimen spontaneously, following a single inhaled dose of INS316 (10 to 180 mg), and following placebo.
Measurements and results: Sputum weight, sputum cell content, spirometry, and oxyhemoglobin saturation. Only 28% of these patients were able to expectorate a macrophage-containing, deep-lung specimen spontaneously or following inhalation of placebo. In contrast, 85% of the patients were able to produce a specimen following inhalation of INS316. The average weight of the sputum expectorated was increased fourfold by placebo and 10-fold by INS316. A mild transient decrease in pulmonary function was observed following INS316 administration.
Conclusion: A single dose of INS316 safely improves the ability of patients with mild chronic bronchitis to expectorate a deep-lung sputum specimen suitable for cytologic evaluation.