Animal models of COPD: What do they tell us?

Abstract

COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanisms and identify biomarkers that may be therapeutic targets that would facilitate the development of improved standard of care. Here, we review the different established animal models of COPD and the various aspects of disease pathophysiology that have been successfully recapitulated in these models including chronic lung inflammation, airway remodelling, emphysema and impaired lung function. Furthermore, some of the mechanistic features, and thus biomarkers and therapeutic targets of COPD identified in animal models are outlined. Some of the existing therapies that suppress some disease symptoms that were identified in animal models and are progressing towards therapeutic development have been outlined. Further studies of representative animal models of human COPD have the strong potential to identify new and effective therapeutic approaches for COPD.

Attenuating immune pathology using a microbial-based intervention in a mouse model of cigarette smoke-induced lung inflammation

“…Acute cigarette smoke exposure can lead to inflammatory responses that may be important preceding events in the chronic changes to lung physiology [32]. The mouse model of acute cigarette smoke exposure used in this study was designed to determine the impact of KB on modulating these earlier alterations in the inflammatory response and not the chronic bronchitic or emphysematous phenotype observed in chronic mouse cigarette smoke exposure models [29, 33–38]. This study therefore focused on outcome measurements that are impacted by acute cigarette smoke exposure, including lung inflammation resulting from smoke-induced tissue damage, systemic inflammation, immune cell activation, and body weight.…”

Modelling COPD co‐morbidities in preclinical models

“…Thus, these studies highlight that chronic exposure to cigarette smoke causes systemic features that closely resemble extrapulmonary manifestations observed in COPD patients, and that these murine models are a useful tool in exploring therapeutics aimed at treating skeletal muscle wasting and dysfunction observed in human COPD. While skeletal muscle wasting and dysfunction is the best developed COPD co‐morbidity in mice, we and others are developing clinically relevant animal models to investigate the link between COPD and cardiovascular, cognitive and metabolic co‐morbidities . A current limitation is that the smoke exposure mouse models do not cause severe COPD, where a complementary genetic susceptibility strategy may be required to develop a more severe model of COPD co‐morbidities.…”

Enhancing tristetraprolin activity reduces the severity of cigarette smoke‐induced experimental chronic obstructive pulmonary disease

“…18,[59][60][61][62] While the impact of treatments on pro-inflammatory cytokine and chemokine mRNA expression levels in the lungs after acute CS exposure was not as striking as the repression in TTP active mouse, BORT + AAL (S) significantly repressed Tnfa mRNA levels after four days, and features of CS-induced airway remodelling at eight weeks were ameliorated. Given that our CS-induced experimental COPD mouse model is corticosteroid resistant, we have discovered that active TTP represses inflammation and the hallmark features of human COPD in vivo when corticosteroids cannot.…”