Airway inflammation in a novel mouse model of asthma-COPD overlap induced by co-exposure to papain and tobacco smoke

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are respiratory diseases associated with airway inflammation, which is the main pathogenesis. Although their causes and characteristics differ, in some cases, asthma and COPD may coexist in the same patient in a condition called asthma-COPD overlap (ACO). The prognosis of ACO is more unfavourable than those of asthma or COPD alone, without any treatment strategies demonstrating efficacy. Owing to its intricate spectrum of features, the detailed pathogenesis of how ACO exacerbates respiratory features remains unclear. In this study, we exposed papain-induced asthma model mice to tobacco smoke to establish an ACO mouse model, in which features of airway inflammation observed in both asthma and COPD were incorporated. This model exhibited distinctive mixed and corticosteroid-resistant airway inflammation and emphysematous changes that are characteristic of ACO. The novel mouse model established here is expected to significantly contribute to elucidating the mechanisms of the broad pathologies of ACO and identifying potential therapeutic targets.