REVIEW PAPER
 
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
Chronic obstructive pulmonary disease (COPD) is a progressive disorder that makes breathing difficult, characterized by chronic bronchitis, mucus hypersecretion, airway remodelling, and emphysema. Although caused by various factors, the leading cause is active or passive cigarette smoking (CS) is. The treatment available provides symptomatic relief and is associated with serious adverse effects, such as cardiovascular events and pneumonia; hence, there is an unmet need for research on drug treatment for COPD. This literature review provides an update on the various animal models of COPD that have been developed by the exposure of CS alone, or in combination with other inducing agents.

Abbreviated description of the state of knowledge:
The combination of SCS/MCS with LPS should be preferred to a single smoke component to induce COPD. It was observed that mouse models are extensively used, C57B1/6 and BALB/c females are more vulnerable to COPD, whereas, in rat models, male SD rats are mostly used. Guinea pigs, due to their anatomical similarity, are found to be a better model that can be used to develop COPD.

Conclusions:
Suitable animal models and validated apparatus are crucial for successful COPD animal model development. Conventionally authenticated research-grade cigarettes should be used for effortless distribution of a specific concentration of total suspended particles (TSP) or total particulate matter (TPM), including nicotine and carbon monoxide. There is also a need to focus on the various types of apparatus to be used for COPD induction in murine models considering optimum exposure, reliability as well as the sturdiness of the apparatus which would provide better execution of the protocol with minimum harm to the experimenter.

 
REFERENCES (57)
1.
Eapen, MS, Hansbro, P.M, Larsson-Callerfelt, AK, Jolly MK, Myers S, Sharma P, Jones B, Rahman MA, Markos J, Chia C, Larby J, Haug G, Hardikar A, Weber HC, Mabeza G, Cavalheri V, Khor YH, McDonald CF, Sohal SS. Chronic Obstructive Pulmonary Disease, and LungCancer: Underlying Pathophysiology and New Therapeutic Modalities. Drugs 2018; 78(16): 1717–1740.
 
2.
Uemasu K, Tanabe N, Tanimura K, Hasegawa K, Mizutani T, Hamakawa Y, Sato S, Ogawa E, Thomas MJ, Ikegami M, Muro S, Hirai T, Sato A. Serine Protease Imbalance in the Small Airways and Development of Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease Serine Protease Imbalance in the Small Airways and Development of Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease. Am J Respir Cell Mol Biol 2020; 63(1): 67–78.
 
3.
Pandey KC, De S, Mishra PK. Role of Proteases in Chronic Obstructive Pulmonary Disease. Front Pharmacol 2017; 8: 1–9.
 
4.
Thimmulappa RK, Chattopadhyay I, Rajasekaran S. Oxidative Stress Mechanisms in the Pathogenesis of Environmental Lung Diseases. Oxidative Stress in Lung Diseases. 2019; 103–137.
 
5.
Zhou A, Luo L, Liu N, Zhang C, Chen Y, Yin Y, Zhang J, He Z, Xie L, Xie J, Li J, Zhou Z, Chen Y, Chen P. Prospective development of practical screening strategies for diagnosis of asthma – COPD overlap. Respirology 2020; 25(7): 735–742.
 
6.
Sim YS, Lee JH, Lee WY, Suh DI, Oh YM, Yoon JS, Lee JH, Cho JH, Kwon CS, Chang JH. Tuberc Respir Dis (Seoul) 2017; 80(2): 105–112.
 
7.
da Costa CH, Noronha Filho AJ, Marques E Silva RMF, da Cruz TF, de Oliveira Monteiro V, Pio M, Rufino RL. Alpha 1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease patients: Is systematic screening necessary? BMC Res Notes. 2019; 12(10): 1–5.
 
8.
Andarian SJ, Olyaeemanesh A, Hosseini SA, Sari AA, Firoozbakhsh S, Jadesi MN, Mobinizadeh M. The safety and effectiveness of the current treatment regimen with or without roflumilast in advanced COPD patients: A systematic review and meta-analysis of randomized controlled trials. Med J Islam Repub Iran. 2016; 30(1): 332.
 
9.
Roche N. Stable COPD Treatment: Where are We?, COPD: Journal of Chronic Obstructive Pulmonary Disease. 2018; 15(2): 123–129.
 
10.
Celli BR, Anderson JA, Cowans NJ, Crim C, Hartley BF, Martinez FJ, Morris AN, Quasny H, Yates J, Vestbo J, Calverley PMA. Pharmacotherapy and Lung Function Decline in Patients with Chronic Obstructive Pulmonary Disease. A Systematic Review. Am J Respir Crit Care Med 2021 Mar 15; 203(6): 689–698.
 
11.
Hough KP, Curtiss ML, Blain TJ, Liu R-M, Trevor J, Deshane JS and Thannickal VJ Airway Remodeling in Asthma. FrontMed. 2020; 7: 191.
 
12.
Sidletskaya K, Vitkina T, Denisenko Y. The role of toll-like receptors 2 and 4 in the pathogenesis of the chronic obstructive pulmonary disease. Int J COPD. 2020; 15: 1481–1493.
 
13.
Lannoy V, Côté-Biron A, Asselin C, Rivard N. Phosphatases in toll-like receptors signaling: the unfairly-forgotten. Cell Commun Signal. 2021; 19(1): 10.
 
14.
Rodríguez-Arce I, Morales X, Ariz M, Euba B, López-López N, Esparza M, Hood DW, Leiva J, Ortíz-de-Solórzano C, Garmendia J. Development and multimodal characterization of an elastase-induced emphysema mouse disease model for the COPD frequent bacterial exacerbator phenotype. Virulence. 2021; 12(1): 1672–1688.
 
15.
Hewitt R, Farne H, Ritchie A, Luke E, Johnston SL, Mallia P. The role of viral infections in exacerbations of chronic obstructive pulmonary disease and asthma. Ther Adv Respir Dis. 2016 Apr; 10(2): 158–74.
 
16.
Chapman KR. Bench to Bedside and Back: The Evolving Story of Alpha-1 Antitrypsin Deficiency. Am J Respir Cell Mol Biol 2021; 63(4): 403–404.
 
17.
Carver PI, Anguiano V, D’Armiento JM, Shiomi T. Mmp1a, and Mmp1b are not functional orthologs to human MMP1 in cigarette smokeinduced lung disease. Exp Toxicol Pathol. 2015 Feb; 67(2): 153–9.
 
18.
Pinkerton KE, Van Winkle LS, Plopper CG, Smiley-Jewell S, Covarrubias EC, McBride JT. Architecture of the tracheobronchial tree. Comp Biol Norm Lung. 2015; 2: 33–51.
 
19.
Ramírez-Ramírez E, Torres-Ramírez A, Alquicira-Mireles J, Cañavera-Constantino A, Segura-Medina P, Montaño-Ramírez M, Ramos-Abraham C, Vargas MH, Arreola-Ramírez JL. Characteristic plethysmographic findings in a guinea pig model of COPD. Exp Lung Res 2017; 43(2): 57–65.
 
20.
Plopper CG, Hyde DM. Epithelial Cells of the Bronchiole. 2nd ed. Parent RA, editor. Comparative Biology of the Normal Lung. Academic Press; 2015. p. 83–92.
 
21.
Gehrig S, Duerr J, Weitnauer M, Wagner CJ, Graeber SY, Schatterny J, Hirtz S, Belaaouaj A, Dalpke AH, Schultz C, Mall MA. Lack of neutrophil elastase reduces inflammation, mucus hypersecretion, and emphysema, but not mucus obstruction, in mice with cystic fibrosis-like lung disease. Am J Respir Crit Care Med. 2014 May 1; 189(9): 1082–92.
 
22.
Horinouchi T, Higashi T, Mazaki Y, Miwa S. Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties. Biol Pharm Bull. 2016; 39(6): 909–14.
 
23.
Ghorani V, Boskabady MH, Khazdair MR, Kianmeher M. Experimental animal models for COPD: a methodological review. Tob Induc Dis 2017; 15(25): 1–13.
 
24.
Reczyńska K, Tharkar P, Kim SY, Wang Y, Pamuła E, Chan HK, Chrzanowski W. Animal models of smoke inhalation injury and related acute and chronic lung diseases. Adv Drug Deliv Rev. 2018; 123: 107–134.
 
25.
Mohammad Y, Shaaban R, Al-Zahab BA, Khaltaev N, Bousquet J, Dubaybo B. Impact of active and passive smoking as risk factors for asthma and COPD in women presenting to primary care in Syria: first report by the WHO-GARD survey group. Int J Chron Obstruct Pulmon Dis. 2013; 8: 473–82.
 
26.
Wang G, Mohammadtursun N, Lv Y, Zhang H, Sun J, Dong J. Baicalin exerts anti-airway inflammation and anti-remodeling effects in the severe stage rat model of chronic obstructive pulmonary disease. Evid. 2018; 1: 1–14.
 
27.
Wang G, Mohammadtursun N, Sun J, Lv Y, Jin H, Lin J, Kong L, Zhao Z, Zhang H, Dong J. Establishment and evaluation of a rat model of sidestream cigarette smoke-induced chronic obstructive pulmonary disease. Front Physiol 2018; 9: 58.
 
28.
Wang L, Kong CC, Chen YR, Fu DY, Li J, Huang CY, Gan GX, Chen BB, Liang M, Xu M, Hu RC, Tan SX, Dal AG. Effect of Atorvastatin on Lung Apoptosis-Associated Protein Caspase-12 in Chronic Obstructive Pulmonary Disease (COPD) Model Rats. J Anesthesiol Pain Res. 2019; 2(1): 10–13.
 
29.
Fricker M, Deane A, Hansbro PM. Animal models of chronic obstructive pulmonary disease. Expert Opin Drug Discov. 2014 Jun; 9(6): 629–45.
 
30.
Sun J, Bao J, Shi Y, Zhang B, Yuan L, Li J, Zhang L, Sun M, Zhang L, Sun W. Effect of simvastatin on MMPs and TIMPs in cigarette smokeinduced rat COPD model. Int J COPD 2017; 12: 717–724.
 
31.
Scott A, Lugg ST, Aldridge K, et al. Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages.Thorax. 2018; 73: 1161–1169.
 
32.
Caia GL, Efimova OV, Velayutham M, El-Mahdy MA, Abdelghany TM, Kesselring E, Petryakov S, Sun Z, Samouilov A, Zweier JL. Organspecific mapping of in vivo redox state in control and cigarette smoke-exposed mice using EPR/NMR co-imaging. J Magn Reson 2012; 216: 21–27.
 
33.
Pan X, Xu K, Li Y, Wang X, Peng X, Li M, Li Y. Interleukin-35 expression protects against cigarette smoke-induced lung inflammation in mice. Biomed Pharmacother 2019; 110: 727–732.
 
34.
Yang Jinho, Kim Eun Kyoung, Park Hyeon Ju, McDowell Andrea, Kim Yoon-Keun. The impact of bacteria-derived ultrafine dust particles on pulmonary diseases. Virulence. 2021; 2(1): 1672–1688.
 
35.
Li C, Yan Y, Shi Q, Kong Y, Gao L, Bao H, Li Y. Recuperating lung decoction attenuates inflammation and oxidation in cigarette smokeinduced COPD in rats via activation of ERK and Nrf2 pathways. Cell Biochem Funct 2017; 35(5): 278–86.
 
36.
Miao L, Gao Z, Huang F, et al. Erythromycin enhances the anti-inflammatory activity of budesonide in COPD rat model. Int J Clin Exp Med 2015; 8(12): 22217–22226.
 
37.
Weng J, Wang Y, Sun TY. Cathelicidin LL-37 restoring glucocorticoid function in smoking and lipopolysaccharide-induced airway inflammation in rats. Chin Med J. 2019; 132(5): 1–8.
 
38.
Miao L, Gao Z, Huang F, Huang S, Zhang R, Ma D, Wu Q, Li F, Chen H, Wang J. Pulmonary Pharmacology & Therapeutics Characteristic comparison of three rat models induced by cigarette smoke or combined with LPS: To establish a suitable model for the study of airway mucus hypersecretion in chronic obstructive pulmonary disease. Pulm Pharmacol Ther 2012; 25: 349–356.
 
39.
Wang XL, Li T, Li JH, Miao SY, Xiao XZ. The Effects of Resveratrol on Inflammation and Oxidative Stress in a Rat Model of Chronic Obstructive Pulmonary Disease longevity. Molecules 2017; 22(9): 1529.
 
40.
Zhang XF, Zhu J, Geng WY, Zhao SJ, Jiang CW, Cai SR, Cheng M, Zhou CY, Liu ZB. Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease. J Integr Med. 2014; 12(5): 417–424.
 
41.
Lee JW, Ryu HW, Park SY, Park HA, Kwon OK, Yuk HJ, Shrestha KK, Park M, Kim JH, Lee S, Oh SR, Ahn KS. Protective effects of neem (Azadirachta indica A. Juss.) leaf extract against cigarette smoke- and lipopolysaccharide-induced pulmonary inflammation. Int J Mol Med. 2017 Dec; 40(6): 1932–1940.
 
42.
Yang Y, Di T, Zhang Z, et al. Dynamic evolution of emphysema and airway remodeling in two mouse models of COPD. BMC Pulm Med. 2021; 21: 134.
 
43.
Lee JW, Ryu HW, Lee SU, Kim MG, Kwon OK, Kim MO, Oh TK, Lee JK, Kim TY, Lee SW, Choi S, Li WY, Ahn KS, Oh SR. Pistacia weinmannifolia ameliorates cigarette smoke and lipopolysaccharide-induced pulmonary inflammation by inhibiting interleukin-8 production and NF-kB activation. Int J Mol Med. 2019; 44(3): 949–959.
 
44.
Cafferkey J, Coultas JA, Mallia P. Human rhinovirus infection and COPD: role in exacerbations and potential for therapeutic targets. Expert Rev Respir Med. 2020; 1–13.
 
45.
Wen wen. Expression of connective tissue growth factor and bone morphogenetic protein-7 in Pseudomonas aeruginosa-induced chronic obstructive pulmonary disease in rats. COPD. 2013; 10(6): 657–666.
 
46.
Foronjy RF, Dabo AJ, Taggart CC, Weldon S, Geraghty P. Respiratory syncytial virus infections enhance cigarette smoke-induced COPD in mice. PLoS One. 2014; 9(2): 90567.
 
47.
Kozma Rde L, Alves EM, Barbosa-de-Oliveira VA, Lopes FD, Guardia RC, Buzo HV, Faria CA, Yamashita C, Cavazzana Júnior M, Frei F, Ribeiro-Paes MJ, Ribeiro-Paes JT. A new experimental model of cigarette smoke-induced emphysema in Wistar rats. JBP. 2014; 40(1): 46–54.
 
48.
Ke Q, Yang L, Cui Q, et al. Ciprofibrate attenuates airway remodeling in cigarette smoke-exposed rats. Respir Physiol Neurobiol. 2020; 271: 1–9.
 
49.
Wang L, Meng J, Wang C, Yang C, Wang Y, Li Y, Li Y. Highlight article:.Hydrogen sulfide alleviates cigarette smoke-induced COPD through inhibition of the TGF-β1/smad pathway. Exp Biol Med. 2020; 245(3): 190–200.
 
50.
Luo F, Liu J, Yan T, Miao M. Salidroside alleviates cigarette smoke-induced COPD in mice. Biomed Pharmacother 2017; 86: 155–161.
 
51.
Yu D, Liu X, Zhang G, Ming Z, Wang T. Isoliquiritigenin inhibits cigarette smoke-induced COPD by attenuating inflammation and oxidative stress via the regulation of the Nrf2 and NF-κB signaling pathways. Front Pharmacol 2018; 9: 1–8.
 
52.
Nie YC, Wu H, Li PB, Luo YL, Long K, Xie LM, Shen JG, Su WW. J Med Food. 2012; 15: 894–900.
 
53.
Li Y, Gu C, Xu W, Yan J, Xia Y, Ma Y, Chen C, He X, Tao H. Therapeutic effects of amniotic fluid-derived mesenchymal stromal cells on lung injury in rats with emphysema. Respir Res. 2014; 15: 1–14.
 
54.
Possebon L, de Souza Lima Lebron I, Furlan da Silva L, Tagliaferri Paletta J, Glad BG, Sant’Ana M, Iyomasa-Pilon MM, Ribeiro Souza H, de Souza Costa S, Pereira da Silva Rodriguesa G, Pereira ML, de Haro Moreno A, Girol AP. Anti-inflammatory actions of herbal medicines in a model of chronic obstructive pulmonary disease induced by cigarette smoke. Biomed Pharmacother. 2018; 99: 591–597.
 
55.
Dianat M, Radan M, Badavi M, Mard SA, Bayati V, Ahmadizadeh M. Crocin attenuates cigarette smoke-induced lung injury and cardiac dysfunction by anti-oxidative effects: the role of Nrf2 antioxidant system in preventing oxidative stress. Respiratory research. 2018; 19(1): 58.
 
56.
Shen Y, Huang S, Kang J, Lin J, Lai K, Sun Y, Xiao W, Yang L, Yao W, Cai S, Huang K, Wen F. Management of airway mucus hypersecretion in chronic airway inflammatory disease: Chinese expert consensus (English edition). Int J Chron Obstruct Pulmon Dis. 2018; 13: 399–407.
 
57.
Liang G-B, He Z-H. Animal models of emphysema. Chin Med. 2019; 132(20): 2465–2475.
 
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