Animal models of chronic obstructive pulmonary disease and their role in drug discovery and development: a critical review

INTRODUCTION: The use of laboratory animals is essential to understand the mechanisms underlying COPD and to discover and evaluate new drugs. However, the complex changes associated with the disease in humans are difficult to fully replicate in animal models. AREAS COVERED: This review examines the most recent literature on animal models of COPD and their implications for drug discovery and development. EXPERT OPINION: Recent advances in animal models include the introduction of transgenic mice with an increased propensity to develop COPD-associated features, such as emphysema, and animals exposed to relevant environmental agents other than cigarette smoke, in particular biomass smoke and other air pollutants. Other animal species, including zebrafish, pigs, ferrets and non-human primates, are also increasingly being used to gain insights into human COPD. Furthermore, three-dimensional organoids and humanized mouse models are emerging as technologies for evaluating novel therapeutics in more human-like models. However, despite these advances, no model has yet fully captured the heterogeneity and progression of COPD as observed in humans. Therefore, further research is needed to develop improved models incorporating humanized elements in experimental animals, that may better predict therapeutic responses in clinic settings and accelerate the development of new treatments for this debilitating disease.