Skip to main content
Duke University Libraries
DukeSpace Scholarship by Duke Authors
  • Login
  • Ask
  • Menu
  • Login
  • Ask a Librarian
  • Search & Find
  • Using the Library
  • Research Support
  • Course Support
  • Libraries
  • About
View Item 
  •   DukeSpace
  • Duke Scholarly Works
  • Research and Writings
  • View Item
  •   DukeSpace
  • Duke Scholarly Works
  • Research and Writings
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Effect of the S-nitrosoglutathione reductase inhibitor N6022 on bronchial hyperreactivity in asthma.

Thumbnail
View / Download
491.7 Kb
Date
2018-06
Authors
Que, Loretta G
Yang, Zhonghui
Lugogo, Njira L
Katial, Rohit K
Shoemaker, Steven A
Troha, Janice M
Rodman, David M
Tighe, Robert M
Kraft, Monica
Show More
(9 total)
Repository Usage Stats
102
views
16
downloads
Abstract
<h4>Rationale</h4>Patients with asthma demonstrate depletion of the endogenous bronchodilator GSNO and upregulation of GSNOR.<h4>Objectives</h4>An exploratory proof of concept clinical study of N6022 in mild asthma to determine the potential bronchoprotective effects of GSNOR inhibition. Mechanistic studies aimed to provide translational evidence of effect.<h4>Methods</h4>Fourteen mild asthma patients were treated with intravenous N6022 (5 mg) or placebo and observed for 7 days, with repeated assessments of the provocative dose of methacholine causing a 20% fall in FEV1 (methacholine PC20 FEV1), followed by a washout period and crossover treatment and observation. In vitro studies in isolated eosinophils investigated the effect of GSNO and N6022 on apoptosis.<h4>Measurements and main results</h4>This was a negative trial as it failed to reach its primary endpoint, which was change from baseline in methacholine PC20 FEV1 at 24 h. However, our exploratory analysis demonstrated significantly more two dose-doubling increases in PC20 FEV1 for N6022 compared with placebo (21% vs 6%, P < 0.05) over the 7-day observation period. Furthermore, a significant treatment effect was observed in the change in PC<sub>20</sub> FEV1 from baseline averaged over the 7-day observation period (mean change: +0.82 mg/ml [N6022] from 1.34 mg/ml [baseline] vs -0.18 mg/ml [placebo] from 1.16 mg/ml [baseline], P = 0.023). N6022 was well tolerated in mild asthmatics. In vitro studies demonstrated enhanced eosinophilic apoptosis with N6022.<h4>Conclusions</h4>In this early phase exploratory proof of concept trial in asthma, N6022 did not significantly alter methacholine PC20 FEV1 at 24 h, but did have a treatment effect at 7 days compared to baseline. Further investigation of the efficacy of S-nitrosoglutathione reductase inhibition in a patient population with eosinophilic asthma is warranted.
Type
Journal issue
Subject
Humans
Asthma
Bronchial Hyperreactivity
Benzamides
Methacholine Chloride
S-Nitrosoglutathione
Pyrroles
Aldehyde Oxidoreductases
Bronchoconstrictor Agents
Placebos
Bronchial Provocation Tests
Forced Expiratory Volume
Treatment Outcome
Cross-Over Studies
Double-Blind Method
Adult
Middle Aged
Female
Male
Young Adult
Administration, Intravenous
Proof of Concept Study
Permalink
https://hdl.handle.net/10161/22236
Published Version (Please cite this version)
10.1002/iid3.220
Collections
  • Research and Writings
More Info
Show full item record

Scholars@Duke

Kraft

Monica Kraft

Adjunct Professor in the Department of Medicine
Lugogo

Njira Lucia Lugogo

Adjunct Assistant Professor in the Department of Medicine
My research focus is asthma. I perform clinical trials in asthma and I am interested in working on new therapies for patients with severe asthma.  I am also interested in the role of obesity on asthma phenotypes and biomarkers.
Que

Loretta Georgina Que

Professor of Medicine
My research interests focus on studying the role of nitric oxide and related enzymes in the pathogenesis of lung disease, specifically that caused by nitrosative/oxidative stress. Proposed studies are performed in cell culture and applied to animal models of disease, then examined in human disease where relevant. It is our hope that by better understanding the role of NO and reactive nitrogen species in mediating inflammation, and regulating cell signaling, that we will not only help to unravel
Tighe

Robert Matthew Tighe

Associate Professor of Medicine
The research focus of the Tighe laboratory is performing pulmonary basic-translational studies to define mechanisms of susceptibility to lung injury and disease. There are three principal focus areas. These include: 1) Identifying susceptibility factors and candidate pathways relevant to host biological responses to environmental pollutants such as ozone, woodsmoke and silica, 2) Defining protective and detrimental functions of lung macrophage subsets and their cross talk with the epithelium
Alphabetical list of authors with Scholars@Duke profiles.

Material is made available in this collection at the direction of authors according to their understanding of their rights in that material. You may download and use these materials in any manner not prohibited by copyright or other applicable law.

Rights for Collection: Research and Writings


Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info

Make Your Work Available Here

How to Deposit

Browse

All of DukeSpaceCommunities & CollectionsAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit DateThis CollectionAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit Date

My Account

LoginRegister

Statistics

View Usage Statistics
Duke University Libraries

Contact Us

411 Chapel Drive
Durham, NC 27708
(919) 660-5870
Perkins Library Service Desk

Digital Repositories at Duke

  • Report a problem with the repositories
  • About digital repositories at Duke
  • Accessibility Policy
  • Deaccession and DMCA Takedown Policy

TwitterFacebookYouTubeFlickrInstagramBlogs

Sign Up for Our Newsletter
  • Re-use & Attribution / Privacy
  • Harmful Language Statement
  • Support the Libraries
Duke University