An Asthma-COPD Overlap Mouse Model Establishment

<bold>Background:</bold> Nowadays, specific pathogenesis about asthma-COPD overlap (ACO) is not yet known due to limited clinical research and lacking of reliable animal model. <bold>Aims:</bold> To establish an asthma-COPD overlap (ACO) mouse model, discover disease characteristics and immunology phenotypes, and explore its potential pathogenesis. <bold>Methods:</bold> We developed a mouse model of ACO by exposing to cigarette smoke or nano carbon black (nCB) and Proteinase from Aspergillus Melleus (PAM). To confirm characteristics of asthma and emphysema via micro-CT and airway hyperresponsiveness (AHR). Cell classification and flow cytometry were used to measure inflammatory cells in bronchoalveolar lavage and lung. <bold>Results:</bold> When exposed to inhaled smoke/nCB and PAM, C57BL/6 mice developed both emphysema and asthma, including more lung destruction, increased respiratory system resistance and eosinophils, even though the AHR of overlap group was mildly lower than asthma only. Besides, transcription factors GATA3 and RORγt expressed more in T helper (Th) cells of lung, especially the latter one had synergistic effect for emphysema and asthma. <bold>Conclusions:</bold> Mice developed Th17 dependent ACO via exposure to both tobacco smoke/nCB and PAM, while Th2 induced asthma is weakened by cigarette components. We elucidate dynamic changes in immunological response of ACO for the first time, preliminarily exploring the underlying immunology mechanism, which would help to yield improved diagnostic and therapeutic strategies.