Prospects for macrolide therapy of asthma and COPD

Michael J. Parnham*, Virginia Norris, Jennifer A. Kricker, Thorarinn Gudjonsson, Clive P. Page

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Macrolide compounds, many of which are derived from natural sources, all share a lactone ring structure, but of varying sizes. Their biological activities differ with structure and size but tend to overlap. Marketed macrolide drugs include immunosuppressives and antibiotics. Some of the latter have been shown to exert anti-inflammatory activities, due to direct effects on inflammatory cells and processes when used for respiratory infections. Consequently, azithromycin is included in clinical guidelines for COPD and asthma treatment, though it has the disadvantage, as an antibiotic, of increasing bacterial resistance. COPD and asthma, however, like several chronic inflammatory diseases involving other organs, are driven to a large extent by epithelial barrier dysfunction. Recently, azithromycin was shown to directly enhance epithelial barrier function and a new class of derivatives, barriolides, is under development with the lead indication COPD. It is thus likely that by circumventing antibiosis and acting on a crucial etiological disease process, this type of agent will open up a new, safer approach to COPD and asthma therapy with macrolides.

Original languageEnglish
Title of host publicationAdvances in Pharmacology
PublisherAcademic Press Inc.
Pages83-110
Number of pages28
ISBN (Print)9780443188800
DOIs
Publication statusPublished - 29 Jul 2023

Publication series

NameAdvances in Pharmacology
Volume98
ISSN (Print)1054-3589
ISSN (Electronic)1557-8925

Bibliographical note

Funding Information:
We thank Dr Peter Teodorovic for preparing the figure with the macrolide chemical structures. All the authors are either employees of (MP, VN, JK) or working with (TG, CP) EpiEndo Pharmaceuticals ehf.

Publisher Copyright:
© 2023

Other keywords

  • Asthma
  • Azithromycin
  • Barriolides
  • COPD
  • Epithelial barrier
  • Lung inflammation
  • Macrolides

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