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

Citation

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, New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways, Clinical Science, 133, (14) pp. 1663-1703. ISSN 0143-5221 (2019) [Refereed Article]


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Copyright Statement

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

DOI: doi:10.1042/CS20181009

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:COPD, infections, smoking, asthma, lung cancer, excerbations, epithelium, inflammation, ICS
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Respiratory Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Respiratory System and Diseases (incl. Asthma)
UTAS Author:Atto, B (Miss Brianna Atto)
UTAS Author:Eapen, MS (Mr Mathew Eapen)
UTAS Author:Sharma, P (Dr Pawan Sharma)
UTAS Author:Markos, J (Dr Jim Markos)
UTAS Author:Larby, J (Dr Josie Larby)
UTAS Author:Haug, G (Dr Greg Haug)
UTAS Author:Weber, HC (Dr Heinrich Weber)
UTAS Author:Mabeza, G (Dr Fungai Mabeza)
UTAS Author:Tristram, S (Dr Stephen Tristram)
UTAS Author:Myers, S (Dr Stephen Myers)
UTAS Author:Geraghty, DP (Professor Dominic Geraghty)
UTAS Author:Flanagan, K (Dr Katie Flanagan)
UTAS Author:Sohal, SS (Dr Sukhwinder Sohal)
ID Code:134125
Year Published:2019
Web of Science® Times Cited:1
Deposited By:Health Sciences
Deposited On:2019-07-29
Last Modified:2019-08-20
Downloads:0

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