title: Preclinical murine models of Chronic Obstructive Pulmonary Disease.
abstract: Chronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and is the 4th leading cause of death worldwide. It is believed that an exaggerated inflammatory response to cigarette smoke causes progressive airflow limitation. This inflammation, where macrophages, neutrophils and T lymphocytes are prominent, leads to oxidative stress, emphysema, small airway fibrosis and mucus hypersecretion. Much of the disease burden and health care utilisation in COPD is associated with the management of its comorbidities and infectious (viral and bacterial) exacerbations (AECOPD). Comorbidities, defined as other chronic medical conditions, in particular skeletal muscle wasting and cardiovascular disease markedly impact on disease morbidity, progression and mortality. The mechanisms and mediators underlying COPD and its comorbidities are poorly understood and current COPD therapy is relatively ineffective. Thus, there is an obvious need for new therapies that can prevent the induction and progression of COPD and effectively treat AECOPD and comorbidities of COPD. Given that access to COPD patients can be difficult and that clinical samples often represent a "snapshot" at a particular time in the disease process, many researchers have used animal modelling systems to explore the mechanisms underlying COPD, AECOPD and comorbidities of COPD with the goal of identifying novel therapeutic targets. This review highlights the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure and the recent advances in modelling infectious exacerbations and comorbidities of COPD.
authors.affiliation: School of Health Sciences, Health Innovations Research Institute, RMIT University, PO Box 71, Bundoora, VIC 3083, Australia; Lung Health Research Centre, Department of Pharmacology & Therapeutics, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: ross.vlahos@rmit.edu.au.
authors.forename: Ross
authors.initials: R
authors.lastname: Vlahos
authors.affiliation: School of Health Sciences, Health Innovations Research Institute, RMIT University, PO Box 71, Bundoora, VIC 3083, Australia; Lung Health Research Centre, Department of Pharmacology & Therapeutics, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Bozinovski
mesh_terms: D000818:Animals; D002100:Cachexia / Q000150:complications; D002318:Cardiovascular Diseases / Q000150:complications; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D018384:Oxidative Stress / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000209:etiology* / Q000276:immunology / Q000382:microbiology
chemical_list: D016207:Cytokines
keywords: AECOPD; COPD; Comorbidities; Emphysema; Lung inflammation