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New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways

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Atto, B, Eapen, MS, Sharma, P, Frey, U, Ammit, AJ, Markos, J, Chia, C, Larby, J, Haug, G, Weber, HC, Mabeza, G, Tristram, S ORCID: 0000-0002-8485-0322, Myers, S ORCID: 0000-0003-4793-3820, Geraghty, DP ORCID: 0000-0001-8968-5912, Flanagan, K, Hansbro, PM and Sohal, SS ORCID: 0000-0001-9627-6498 2019 , 'New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways' , Clinical Science, vol. 133, no. 14 , pp. 1663-1703 , doi: 10.1042/CS20181009.

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Abstract

Chronic respiratory diseases are among the leading causes of mortality worldwide, with themajor contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD)drive clinical and functional decline in COPD and are associated with accelerated loss of lungfunction, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEsand consequently constitute a significant comorbidity in COPD. However, current pharmacological interventions are ineffective in preventing infectious exacerbations and their treatment is compromised by the rapid development of antibiotic resistance. Thus, alternativepreventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infectionof surrounding structures. Thus, disruption of bacterial–host cell interactions with receptorantagonists or modulation of the ensuing inflammatory profile present attractive avenues fortherapeutic development. This review explores key mediators of pathogen–host interactionsthat may offer new therapeutic targets with the potential to prevent viral/bacterial-mediatedAECOPD. There are several conceptual and methodological hurdles hampering the development of new therapies that require further research and resolution.

Item Type: Article
Authors/Creators:Atto, B and Eapen, MS and Sharma, P and Frey, U and Ammit, AJ and Markos, J and Chia, C and Larby, J and Haug, G and Weber, HC and Mabeza, G and Tristram, S and Myers, S and Geraghty, DP and Flanagan, K and Hansbro, PM and Sohal, SS
Keywords: COPD, infections, smoking, asthma, lung cancer, excerbations, epithelium, inflammation, ICS
Journal or Publication Title: Clinical Science
Publisher: Portland Press
ISSN: 0143-5221
DOI / ID Number: 10.1042/CS20181009
Copyright Information:

©2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society

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