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Review
. 2020;12(3):203-225.
doi: 10.1159/000502489. Epub 2019 Sep 17.

Animal Models Reflecting Chronic Obstructive Pulmonary Disease and Related Respiratory Disorders: Translating Pre-Clinical Data into Clinical Relevance

Lloyd Tanner  1 , Andrew Bruce Single  2
Affiliations
Review

Animal Models Reflecting Chronic Obstructive Pulmonary Disease and Related Respiratory Disorders: Translating Pre-Clinical Data into Clinical Relevance

Lloyd Tanner et al. J Innate Immun. 2020.

Abstract

Chronic obstructive pulmonary disease (COPD) affects the lives of an ever-growing number of people worldwide. The lack of understanding surrounding the pathophysiology of the disease and its progression has led to COPD becoming the third leading cause of death worldwide. COPD is incurable, with current treatments only addressing associated symptoms and sometimes slowing its progression, thus highlighting the need to develop novel treatments. However, this has been limited by the lack of experimental standardization within the respiratory disease research area. A lack of coherent animal models that accurately represent all aspects of COPD clinical presentation makes the translation of promising in vitrodata to human clinical trials exceptionally challenging. Here, we review current knowledge within the COPD research field, with a focus on current COPD animal models. Moreover, we include a set of advantages and disadvantages for the selection of pre-clinical models for the identification of novel COPD treatments.

Keywords: Animal models; Chronic obstructive pulmonary disease; Fibrosis; Inflammation; Treatment.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
COPD state versus healthy lung tissue. Inhaled irritants (predominantly CS or fumes from biomass fuels) cause a chronic inflammatory state at different levels of the airways. In the bronchi this may lead to chronic bronchitis, in the bronchioles it causes bronchiolitis, and in the terminal airways and alveoli causes impaired gas exchange due to emphysema. High proteolytic activity results in mucus-hypersecretion and remodeling. The latter causes emphysema (reducing the area available for gas exchange) and a lack of recoil (limiting the expiratory airflow and causing hyperinflation of the lungs).
Fig. 2
Fig. 2
Molecular mechanisms of COPD development (adapted from Linden et al. [105]). MIG, monokine induced by interferon-γ; LTB4, leukotriene B4; CTGF, connective tissue growth factor; IP10, interferon-γ-induced protein 10; I-TAC, IFN-inducible T cell α-chemoattractant.
Fig. 3
Fig. 3
Commonly utilized animal models of COPD/fibrosis.
Fig. 4
Fig. 4
Determining the clinical importance of assay inclusion in a drug discovery cascade. PK, pharmacokinetic; PD, pharmacodynamic.
See this image and copyright information in PMC

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