Abstract：Objective: To compare the differences in terms of airway responsiveness,airway inflammation and pathology among three cough variant asthma (CVA) guinea pig models,and to explore appropriate evaluation criteria to evaluate the advantages and disadvantages of each model. Methods: Three-week-old male Hartley guinea pigs were randomly divided into normal control group,model A group,model B group and model C group. Based on the classical asthmatic guinea pig modeling method,model A was given a reduced dose of ovalbumin during two sensitizations,model C was given cyclophosphamide prior to sensitization to reduce the sensitization state,while model B was given a combination of intra-peritoneal and intramuscular injections,the concentration of ovalbumin was doubled and sensitized once. After 2 weeks,three groups of guinea pigs were nebulized with 1% OVA. The number of capsaicin-induced coughs,changes in airway resistance,the percentage of eosinophils in alveolar lavage fluid and the pathological changes of lung tissue were observed in each group after nebulization. Results: Compared with the normal control group,the cough frequency of guinea pigs in model A,B and C groups was significantly increased,and the difference was statistically significant (P<0.05),but the cough frequency between the three model groups was not statistically significant (P>0.05). During the experimental observation,2 guinea pigs in both model A and model B had obvious wheezing cough respectively. When airway hyperresponsiveness in the guinea pigs was set at the dose of MeCh 0.04 mg/mL,the airway resistance was higher in group A than in group B than in group C (P<0.05). Compared with the normal control group,the percentage of eosinophils in the bronchoalveolar lavage fluid (BALF) of guinea pigs in the three model groups was significantly increased (P<0.05),with a significant increase in model B,but there was no significant difference between the three model groups (P=0.051). In each model group,the local mucosal epithelial injury in the bronchial wall of guinea pigs in each model group was shed off,congestion,edema and infiltration of a large number of inflammatory cells were observed in all layers of the bronchial wall. According to the pathological grading score of guinea pig lungs,the lung histopathological score of guinea pigs in the three model groups was significantly increased (P<0.05),but there was no statistically significant difference between the groups (P>0.05). Conclusion: The cough symptoms and airway hyperresponsiveness of the three models are roughly consistent with the characteristics of clinical symptoms of CVA. Amongst them,there were four guinea pigs in model A and model B with obvious wheezing. Model C's behavior and airway hyperresponsiveness were more stable,the proportion of eosinophils in BALF,and the pathological results were close to the clinical characteristics of CVA patients. Therefore,we believe that the established model C modeling method is feasible and more optimized.
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2021, Vol. 27 
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