COPD
In the global spectrum of respiratory diseases, chronic obstructive pulmonary disease (COPD) has long ranked among the leading causes of death, characterized by high prevalence, high disability rate, and high risk of acute exacerbation. It is not simply a "chronic bronchitis in the elderly", but a highly heterogeneous group of chronic lung diseases. The prolonged and irreversible airway damage poses significant challenges to clinical treatment. The transition of new drugs and therapies from target discovery to clinical application relies heavily on a stable and reproducible in vivo evaluation system. As a crucial bridge connecting basic mechanism research and clinical translation, COPD animal models are widely used in preclinical efficacy and safety assessments of respiratory pharmacology, anti-inflammatory, airway remodeling, and lung protective drugs.

In this issue, we will delve into the model of Chronic Obstructive Pulmonary Disease (COPD) to aid in the advancement of new drug development and guide clinical trials.

1 What is COPD
Chronic Obstructive Pulmonary Disease (COPD) is a highly heterogeneous chronic airway inflammatory disease. Its typical clinical manifestations include long-term cough, expectoration, shortness of breath after physical activity, and dyspnea, often accompanied by recurrent acute exacerbations. Prolonged illness can also lead to systemic complications, such as skeletal muscle atrophy, cardiovascular damage, and metabolic abnormalities. Based on the airway immune-inflammatory phenotype, it can be divided into two core types: Type 1 (T2-low, type 1 inflammation) and Type 2 enrichment (T2-high, type 2 inflammation enrichment)
Type1（T2-low）COPD
·Classic smoking-related COPD is the mainstream clinical type. It is centered around the activation of the Th1/Th17 immune pathway, driving chronic inflammation primarily characterized by the infiltration of neutrophils and alveolar macrophages;
·The main damage-related molecules are DAMPs such as HMGB1 and ATP. The level of eosinophil infiltration is extremely low, and airway inflammation exhibits typical steroid-resistant characteristics;
·Patients often have a long history of smoking, with persistent airflow limitation, destruction of lung parenchyma, and emphysema as the main pathological changes. Acute exacerbations induced by bacterial infection are more common.
Type 2 enriched (T2-high) COPD
·Special eosinophilic COPD type, accounting for 20% to 40% of clinical COPD patients;
·The core pathogenesis involves the release of alarmin (IL-33, TSLP, IL-25) following airway epithelial injury, which specifically activates the ILC2 and Th2 immune pathways, mediating eosinophil and mast cell infiltration;
·The core characteristics are high airway mucus secretion, airway wall remodeling, and concurrent emphysema lesions, which distinguish it from simple asthma airway lesions;
·This phenotype is highly sensitive to inhaled corticosteroids and T2 targeted biologics, and the risk of acute exacerbation in patients is significantly higher than that in the T2-low phenotype.

2 Comparison of Type 1 and Type 2 enriched COPD animal models

3 Core detection indicators for model evaluation
Histopathological examination
▶ Type1 model
·HE staining reveals extensive alveolar destruction, alveolar septal rupture, and emphysema formation, with airway infiltration primarily consisting of neutrophils and macrophages
·PAS staining indicates that goblet cell hyperplasia in the airway is not obvious, and mucus secretion is reduced
▶ Type2 enrichment model
·HE staining reveals emphysematous lesions accompanied by extensive eosinophil infiltration
·PAS staining reveals significant proliferation of goblet cells in the airway and high expression of mucin MUC5AC
·Masson staining reveals increased collagen deposition in the airway, indicating significant airway remodeling
Molecular testing
▶ Type1 model
·IFN-γ, TNF-α, and IL-17A were significantly upregulated in lung tissue and BALF, while IL-33, IL-5, and IL-13 were downregulated
▶ Type2 enrichment model
·The levels of alarm peptides IL-33, TSLP, and Th2 cytokines IL-4, IL-5, and IL-13 were significantly elevated, while the expression levels of Th1/Th17-related inflammatory factors were low
Pulmonary function test
▶ Both types of models exhibited typical pulmonary function changes consistent with emphysema
·The FEV0.1/FVC ratio has significantly decreased
·Increased dynamic lung compliance
·Increased airway resistance

1 Comparison of three COPD models: CS, CS+LPS, and CS+LPS+PPE
2 The matching of three models with drug development directions
3 Model selection for research objectives
4 Three application scenarios of COPD models

Case sharing on COPD model and drug efficacy evaluation

KCI・KMQ COPD R&D Service Platform has successfully established three COPD models: CS, CS+LPS, and CS+LPS+PPE. It can provide robust support for research into the pathogenesis of COPD, drug development, and safety evaluation of clinical medications.

1 Rat COPD model induced by CS+LPS
data display
·Weight change

·Lung histopathology

2 Mouse COPD model induced by CS+LPS
data display
·Weight change

·Pulmonary function test



3 CS+LPS-induced hamster COPD model
data display
·Weight change

·Lung histopathology: assessment of alveolar and bronchiolar inflammation, as well as goblet cell hyperplasia



4 Rat COPD model induced by CS+LPS+PPE
data display
·Weight change

·Lung histopathology: pathological analysis of lung injury and alveolar wall structural damage


·Goblet cell metaplasia of bronchial epithelium, bronchiectasis, and bronchial wall thickening

·CD68

·MUC5AC/MUC5B

5 Pharmacodynamic evaluation of roflumilast in a COPD mouse model induced by CS+LPS+PPE
Data Display
·Weight change

·Lung histopathology: emphysema, pulmonary bulla, alveolar structural damage

·Inflammatory cell infiltration and fibrosis in the damaged area

·Bronchiectasis


KCI・KMQ Respiratory Disease Pharmacology and Efficacy Evaluation Platform boasts a comprehensive animal model system. The platform has accumulated extensive project experience and can meet diversified research requirements.At present, the company has established extensive long-term cooperation with numerous well-known pharmaceutical enterprises and research institutions at home and abroad, laying a solid foundation for the development of innovative drugs.

The successful establishment of COPD animal models serves as a critical link connecting basic research and clinical application. With stable and reliable characteristics, these models can provide strong support for the investigation of COPD pathogenesis, drug development, and safety evaluation of clinical medications.KCI・KMQ animal disease models play a pivotal role in this field. Supported by professional model establishment and evaluation systems, they continuously deliver robust support to research institutions and pharmaceutical enterprises, jointly accelerating the rapid translation of COPD research from basic understanding to therapeutic breakthroughs.