Chest Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Johnson, F. L.
Right arrow Articles by Shaffer, C. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Johnson, F. L.
Right arrow Articles by Shaffer, C. L.
(Chest. 2002;122:2021-2029.)
© 2002 American College of Chest Physicians

Improved Sputum Expectoration Following a Single Dose of INS316 in Patients With Chronic Bronchitis*

Fred L. Johnson, PhD; James F. Donohue, MD, FCCP and Christy L. Shaffer, PhD

* From Inspire Pharmaceuticals, Inc. (Drs. Johnson and Shaffer), Durham, NC; and Department of Medicine (Dr. Donohue), The University of North Carolina at Chapel Hill, Chapel Hill, NC.

Correspondence to: Fred L. Johnson, PhD, Inspire Pharmaceuticals, Inc., 4222 Emperor Blvd, Ste 470, Durham NC 27703-8466; e-mail: FJohnson{at}inspirepharm.com

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.

Key Words: diagnostic tests • lung neoplasms • mucociliary clearance • purinergic P2 • receptors • uridine triphosphate






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the American College of Chest Physicians.