Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • For authors
    • Instructions for authors
    • Submit a manuscript
    • Author FAQs
    • Open access
    • COVID-19 submission information
  • Alerts
  • Podcasts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • For authors
    • Instructions for authors
    • Submit a manuscript
    • Author FAQs
    • Open access
    • COVID-19 submission information
  • Alerts
  • Podcasts
  • Subscriptions

Treatment options in type-2 low asthma

Timothy S.C. Hinks, Stewart J. Levine, Guy G. Brusselle
European Respiratory Journal 2021 57: 2000528; DOI: 10.1183/13993003.00528-2020
Timothy S.C. Hinks
1Respiratory Medicine Unit and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Nuffield Dept of Medicine, Experimental Medicine, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timothy S.C. Hinks
  • For correspondence: timothy.hinks@ndm.ox.ac.uk
Stewart J. Levine
2National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Stewart J. Levine
Guy G. Brusselle
3Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
4Depts of Epidemiology and Respiratory Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Guy G. Brusselle
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Monoclonal antibodies targeting IgE or the type-2 cytokines interleukin (IL)-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma, respectively. However, these therapies are not appropriate for 30–50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, “type-2 low” asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, yet poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristics of type-2 low asthma and summarise current knowledge on the underlying pathobiological mechanisms, which includes neutrophilic airway inflammation often associated with smoking, obesity and occupational exposures and may be driven by persistent bacterial infections and by activation of a recently described IL-6 pathway. We review the evidence base underlying existing treatment options for specific treatable traits that can be identified and addressed. We focus particularly on severe asthma as opposed to difficult-to-treat asthma, on emerging data on the identification of airway bacterial infection, on the increasing evidence base for the use of long-term low-dose macrolides, a critical appraisal of bronchial thermoplasty, and evidence for the use of biologics in type-2 low disease. Finally, we review ongoing research into other pathways including tumour necrosis factor, IL-17, resolvins, apolipoproteins, type I interferons, IL-6 and mast cells. We suggest that type-2 low disease frequently presents opportunities for identification and treatment of tractable clinical problems; it is currently a rapidly evolving field with potential for the development of novel targeted therapeutics.

Abstract

One-third of severe asthma is type-2 low, presenting a challenge to clinicians. This review provides an overview of the currently available treatment options, other treatable traits and a range of therapies in development. https://bit.ly/2YeNOQd

Footnotes

  • Number 2 in the series “Innovations in asthma and its treatment” Edited by P. O'Byrne and I. Pavord

  • Previous articles in this series: No. 1: Asher MI, García-Marcos L, Pearce NE, et al. Trends in worldwide asthma prevalence. Eur Respir J 2020; 56: 2002094.

  • Author contributions: T.S.C. Hinks, S.J. Levine and G.G. Brusselle jointly conceived the article, conducted the literature review and drafted the manuscript. All authors approved the final manuscript.

  • Conflict of interest: T.S.C. Hinks reports grants from The Wellcome Trust (Wellcome Trust Fellowships 088365/z/09/z, 104553/Z/14/Z, 211050/Z/18/Z) and the Guardians of the Beit Fellowship (Wellcome-Beit Fellowship 211050/Z/18/A), during the conduct of the study; personal fees for lectures from AstraZeneca and TEVA, personal fees for education presentations from Peer Voice, outside the submitted work.

  • Conflict of interest: S.J. Levine has nothing to disclose.

  • Conflict of interest: G.G. Brusselle reports personal fees for advisory board work and lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva, personal fees for advisory board work from Sanofi, outside the submitted work.

  • Support statement: This work was supported by grants from the Wellcome Trust (104553/z/14/z, 211050/Z/18/z) and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) (to T.S.C. Hinks), the Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (to S.J. Levine), and the BOF19/GOA/008 Concerted Research Action of Ghent University. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received March 2, 2020.
  • Accepted June 1, 2020.
  • The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2021
https://www.ersjournals.com/user-licence
View Full Text

ERS Members

myERS - ERS members : log in with your myERS username and password.

INDIVIDUALS

Log in Login as an individual user.

Forgot your username or password?

LIBRARY USERS

Log in through your institution

If your library has a subscription, you may already be logged in via your IP address. Otherwise you may be able to log in via one of the following routes.
You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.
If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details.
If you think you should have access, please contact your librarian or email journals@ersnet.org

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top
View this article with LENS
Vol 57 Issue 1 Table of Contents
European Respiratory Journal: 57 (1)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Treatment options in type-2 low asthma
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Alerts
Sign In to Email Alerts with your Email Address
Citation Tools
Treatment options in type-2 low asthma
Timothy S.C. Hinks, Stewart J. Levine, Guy G. Brusselle
European Respiratory Journal Jan 2021, 57 (1) 2000528; DOI: 10.1183/13993003.00528-2020

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Treatment options in type-2 low asthma
Timothy S.C. Hinks, Stewart J. Levine, Guy G. Brusselle
European Respiratory Journal Jan 2021, 57 (1) 2000528; DOI: 10.1183/13993003.00528-2020
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Abstract
    • Introduction
    • Mechanisms
    • Current therapeutic options
    • Potential future treatment options
    • Conclusion
    • Shareable PDF
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • Trends in worldwide asthma prevalence
  • The Management of Mild Asthma
Show more Series

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Reviewers
  • CME
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Submit a manuscript
  • ERS author centre

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2021 by the European Respiratory Society