Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease

Abstract Background Features of asthma and chronic obstructive pulmonary disease (COPD) can coexist in the same patient, in a condition termed asthma– chronic obstructive pulmonary disease overlap (ACO). ACO is heterogeneous condition exhibiting various combinations of asthma and COPD features. No c...

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Main Authors: Yong Suk Jo, Chin Kook Rhee, Hyoung Kyu Yoon, Chan Kwon Park, Jeong Uk Lim, An Tai Joon, Jung Hur
Format: Article
Language:English
Published: BMC 2022-12-01
Series:Journal of Inflammation
Subjects:
Online Access:https://doi.org/10.1186/s12950-022-00322-x
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author Yong Suk Jo
Chin Kook Rhee
Hyoung Kyu Yoon
Chan Kwon Park
Jeong Uk Lim
An Tai Joon
Jung Hur
author_facet Yong Suk Jo
Chin Kook Rhee
Hyoung Kyu Yoon
Chan Kwon Park
Jeong Uk Lim
An Tai Joon
Jung Hur
author_sort Yong Suk Jo
collection DOAJ
description Abstract Background Features of asthma and chronic obstructive pulmonary disease (COPD) can coexist in the same patient, in a condition termed asthma– chronic obstructive pulmonary disease overlap (ACO). ACO is heterogeneous condition exhibiting various combinations of asthma and COPD features. No clinically acceptable experimental model of ACO has been established. We aimed to establish an animal model of ACO. Methods We generated two phenotypes of ACO by administering ovalbumin and porcine pancreatic elastase in combination, and papain. The proinflammatory cytokines and cell types in bronchoalveolar lavage fluid (BALF) were investigated, and lung function parameters were measured using the FlexiVent system. Results Greater airway inflammation was observed in the asthma and both ACO models, and emphysema was found in the COPD and both ACO models. The proportion of eosinophils in BALF was elevated in the asthma and ACO-a model. Type 2 inflammatory cytokine levels were highest in the ACO-a model, and the neutrophil gelatinase–associated lipocalin level was elevated in the asthma and ACO-a model. Of lung function parameters, compliance was greater in the COPD and ACO-b model, in which elastance was lower than in the asthma model. Airway resistance increased with the methacholine concentration in the asthma and both ACO models, but not in the control or COPD model. Conclusion We established two murine models of ACO that exhibit features of asthma and COPD. We validated the clinical relevance of the ACO models based on changes in cytokine profiles and lung function. These models will be useful in further studies of the pathogenesis of, and therapeutic targets for ACO.
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spelling doaj.art-f8946a656b1142bf8e1f86d5a44a9f222022-12-22T02:56:26ZengBMCJournal of Inflammation1476-92552022-12-0119111010.1186/s12950-022-00322-xEvaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary diseaseYong Suk Jo0Chin Kook Rhee1Hyoung Kyu Yoon2Chan Kwon Park3Jeong Uk Lim4An Tai Joon5Jung Hur6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaAbstract Background Features of asthma and chronic obstructive pulmonary disease (COPD) can coexist in the same patient, in a condition termed asthma– chronic obstructive pulmonary disease overlap (ACO). ACO is heterogeneous condition exhibiting various combinations of asthma and COPD features. No clinically acceptable experimental model of ACO has been established. We aimed to establish an animal model of ACO. Methods We generated two phenotypes of ACO by administering ovalbumin and porcine pancreatic elastase in combination, and papain. The proinflammatory cytokines and cell types in bronchoalveolar lavage fluid (BALF) were investigated, and lung function parameters were measured using the FlexiVent system. Results Greater airway inflammation was observed in the asthma and both ACO models, and emphysema was found in the COPD and both ACO models. The proportion of eosinophils in BALF was elevated in the asthma and ACO-a model. Type 2 inflammatory cytokine levels were highest in the ACO-a model, and the neutrophil gelatinase–associated lipocalin level was elevated in the asthma and ACO-a model. Of lung function parameters, compliance was greater in the COPD and ACO-b model, in which elastance was lower than in the asthma model. Airway resistance increased with the methacholine concentration in the asthma and both ACO models, but not in the control or COPD model. Conclusion We established two murine models of ACO that exhibit features of asthma and COPD. We validated the clinical relevance of the ACO models based on changes in cytokine profiles and lung function. These models will be useful in further studies of the pathogenesis of, and therapeutic targets for ACO.https://doi.org/10.1186/s12950-022-00322-xAsthmaChronic obstructive pulmonary diseaseExperimental modelCytokineLung function
spellingShingle Yong Suk Jo
Chin Kook Rhee
Hyoung Kyu Yoon
Chan Kwon Park
Jeong Uk Lim
An Tai Joon
Jung Hur
Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
Journal of Inflammation
Asthma
Chronic obstructive pulmonary disease
Experimental model
Cytokine
Lung function
title Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
title_full Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
title_fullStr Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
title_full_unstemmed Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
title_short Evaluation of asthma–chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
title_sort evaluation of asthma chronic obstructive pulmonary disease overlap using a mouse model of pulmonary disease
topic Asthma
Chronic obstructive pulmonary disease
Experimental model
Cytokine
Lung function
url https://doi.org/10.1186/s12950-022-00322-x
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