Tiantian Feng ¹ Juan Cao ¹ Xiaoting Ma ¹ Xinhua Wang ¹ Xiaolong Guo ¹ Na Yan ¹ Chunling Fan ² Shisan (Bob) Bao ^3* Jingchun Fan ¹

• ¹ Gansu University of Chinese Medicine, Lanzhou, Gansu, China
• ² Gansu Provincial Hospital, Lanzhou, Gansu Province, China
• ³ Pathology, The University of Sydney, Darlington, NSW, Australia

Objective: Experimental animal models have been used for decades to study the development and progression of chronic obstructive pulmonary disease (COPD). However, there is a lack of methods for constructing animal models of COPD for optimal modelling. This systematic review aims to assess the various methods used to establish COPD animal models, highlight their advantages and limitations, and explore more optimized approaches for establishing such models. Methods: A systematic search was performed in four English databases (PubMed, Embase, Web of Science, The Cochrane Library) and four Chinese databases (Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database). Out of 8015 retrieved full-text manuscripts, 453 were selected. Results: Smoking (n=140), smoking combined with LPS (n=275), smoking combined with PPE (n=10), smoking combined with bacteria (n=23), and smoking combined with particulate matter (PM2.5) (n=5) were the most used methods for establishing animal models of COPD. Rats and mice were the most frequently selected experimental animals, with male animals accounting for 79.47% of the total. 92.49% or 29.14% of the papers considered lung pathology of experimental animals only or lung pathology and lung function tests, respectively. Conclusions: Our review suggests that the best way to establish an animal model of COPD is to combine smoking with LPS. Although findings from animal models of COPD cannot be directly extrapolated to human COPD, they could provide useful tools for further investigation into human COPD disease.