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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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posted on 2023-05-20, 05:55 authored by Brianna AttoBrianna Atto, Mathew Eapen, Sharma, P, Frey, U, Ammit, AJ, Markos, J, Chia, C, Josie LarbyJosie Larby, Haug, G, Heinrich WeberHeinrich Weber, Fungai Mabeza, Stephen TristramStephen Tristram, Stephen MyersStephen Myers, Dominic GeraghtyDominic Geraghty, Katie FlanaganKatie Flanagan, Hansbro, PM, Sukhwinder SohalSukhwinder Sohal
Chronic respiratory diseases are among the leading causes of mortality worldwide, with the major 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 lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and 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, alternative preventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infection of surrounding structures. Thus, disruption of bacterial–host cell interactions with receptor antagonists or modulation of the ensuing inflammatory profile present attractive avenues for therapeutic development. This review explores key mediators of pathogen–host interactions that may offer new therapeutic targets with the potential to prevent viral/bacterial-mediated AECOPD. There are several conceptual and methodological hurdles hampering the development of new therapies that require further research and resolution.

Funding

Rebecca L Cooper Medical Research Foundation

History

Publication title

Clinical Science

Volume

133

Issue

14

Pagination

1663-1703

ISSN

0143-5221

Department/School

School of Health Sciences

Publisher

Portland Press

Place of publication

59 Portland Place, London, England, W1N 3Aj

Rights statement

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

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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