Airway Eosinophilopoietic and Autoimmune Mechanisms of Eosinophilia in Severe Asthma

Eosinophils are critical in asthma biology, contributing to symptoms, airflow obstruction, airway hyperresponsiveness, and remodeling. In severe asthma, in addition to local maturation in bone marrow, in situ eosinophilopoiesis plays a key role in the persistence of airway eosinophilia. Local milieu of structural, epithelial and inflammatory cells contribute by generating eosinophilopoietic cytokines in response to epithelial-derived alarmins. Another mechanism of persistent airway eosinophilia is glucocorticosteroid insensitivity, which is linked to recurrent airway infections and presence of local autoantibodies. Novel molecules are being developed to target specific immune pathways as potential steroid-sparing strategies.