Underlying Mechanism Suggested by the ACO Model: What Is the Lesson Learned from the Model?

The coexistence of asthma and chronic obstructive pulmonary disease (COPD) is known as asthma–COPD overlap (ACO). Because of the rapid disease progression, frequent and severe exacerbation, and increased comorbidities compared with asthma or COPD alone, the pathogenesis of ACO is believed to be different from each of these respiratory diseases. Because appropriate animal models are lacking, the pathogenesis of ACO including its exacerbation has not been elucidated. We previously developed a well-established murine model that showed the important clinical features of ACO via weekly intratracheal administration of papain in aerosol form in wild-type mice. In this chapter, we describe the phenotype of our single-agent-induced ACO mouse model and knowledge obtained from this model to date. Furthermore, we discuss what should be done in future research using this model to elucidate the pathological processes and identify the diagnostic markers or therapeutic targets of ACO.