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

Atto, B; Eapen, MS; Sharma, P; Frey, U; Ammit, AJ; Markos, J; Chia, C; Larby, J; Haug, G; Weber, HC; Mabeza, G; Tristram, S; Myers, S; Geraghty, DP; Flanagan, KL; Hansbro, PM; Sohal, SS

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

Atto, B

Eapen, MS

Sharma, P

Frey, U Ammit, AJ

Markos, J Chia, C Larby, J Haug, G Weber, HC Mabeza, G Tristram, S Myers, S Geraghty, DP Flanagan, KL Hansbro, PM

Sohal, SS

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Publication Type:: Journal Article
Citation:: Clinical Science, 2019, 133 (14), pp. 1663 - 1703
Issue Date:: 2019-07-31

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Field	Value	Language
dc.contributor.author	Atto, B https://orcid.org/0000-0002-3344-9328	en_US
dc.contributor.author	Eapen, MS https://orcid.org/0000-0003-0570-7059	en_US
dc.contributor.author	Sharma, P https://orcid.org/0000-0002-2904-2306	en_US
dc.contributor.author	Frey, U	en_US
dc.contributor.author	Ammit, AJ https://orcid.org/0000-0003-0555-2544	en_US
dc.contributor.author	Markos, J	en_US
dc.contributor.author	Chia, C	en_US
dc.contributor.author	Larby, J	en_US
dc.contributor.author	Haug, G	en_US
dc.contributor.author	Weber, HC	en_US
dc.contributor.author	Mabeza, G	en_US
dc.contributor.author	Tristram, S	en_US
dc.contributor.author	Myers, S	en_US
dc.contributor.author	Geraghty, DP	en_US
dc.contributor.author	Flanagan, KL	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Sohal, SS https://orcid.org/0000-0002-1650-8613	en_US
dc.date.available	2019-06-28	en_US
dc.date.issued	2019-07-31	en_US
dc.identifier.citation	Clinical Science, 2019, 133 (14), pp. 1663 - 1703	en_US
dc.identifier.issn	0143-5221	en_US
dc.identifier.uri	http://hdl.handle.net/10453/134927
dc.description.abstract	© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society 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.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1156589
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1138402
dc.relation	http://purl.org/au-research/grants/arc/DP190100091
dc.relation.ispartof	Clinical Science	en_US
dc.relation.isbasedon	10.1042/CS20181009	en_US
dc.subject.classification	Cardiovascular System & Hematology	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Bacterial Infections	en_US
dc.subject.mesh	Virus Diseases	en_US
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive	en_US
dc.subject.mesh	Cell Adhesion Molecules	en_US
dc.subject.mesh	Anti-Bacterial Agents	en_US
dc.subject.mesh	Antiviral Agents	en_US
dc.title	New therapeutic targets for the prevention of infectious acute exacerbations of COPD: Role of epithelial adhesion molecules and inflammatory pathways	en_US
dc.type	Journal Article
utslib.citation.volume	14	en_US
utslib.citation.volume	133	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	14	en_US
pubs.publication-status	Published	en_US
pubs.volume	133	en_US

Abstract:

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

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http://hdl.handle.net/10453/134927