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Asthma endotypes are constantly evolving. Currently, there are no universally accepted criteria to define endotypes. The TH2-high endotype can have either allergic or nonallergic underpinnings and is typically characterized by some degree of eosinophilic airway inflammation. Unbiased clustering analyses have led to the identification of pediatric and adult phenotypes characterized by TH2 inflammation and associated endotypes with eosinophilic inflammation. Aspirin-exacerbated respiratory disease has also long been recognized as a unique asthma phenotype. An approach to identify these groups with biomarkers and subsequently choose a targeted therapeutic modality, particularly in severe disease requiring biologic agents, is outlined.