endotype

An endotype is a subtype of a disease defined by a distinct underlying pathophysiological mechanism or biological pathway that drives the condition. This concept distinguishes endotypes from phenotypes, which group patients by observable characteristics such as symptoms or spirometry without reference to the causal biology. Endotypes are identified through patterns of biomarkers, inflammatory cell profiles, gene expression, or treatment response, and they aim to reflect causal biology rather than outward presentation alone.

The term is widely used in respiratory medicine and immunology, where diseases such as asthma, chronic obstructive pulmonary disease (COPD), and allergic disorders show multiple endotypes. In asthma, a commonly discussed dichotomy is Type 2 (T2) high versus non–T2 endotypes. T2-high endotypes involve activation of T helper 2 cells and innate lymphoid cells type 2, with elevated eosinophils, higher fractional exhaled nitric oxide (FeNO), and increased IL‑4, IL‑5, and IL‑13 signaling. This endotype is associated with a favorable response to corticosteroids and to biologic agents targeting IL‑5, IL‑4/IL‑13, or IgE. Non‑T2 endotypes include neutrophilic or pauci-granulocytic patterns and show more heterogeneous therapeutic responses. In COPD, eosinophilic endotypes defined by elevated eosinophils can influence responsiveness to corticosteroids.

Identification relies on biomarkers (eg, blood or sputum eosinophils, FeNO, IgE), gene expression or proteomic profiles, and systematic evaluation of treatment response. Endotypes can be dynamic and overlapping, and their clinical utility depends on reliable measurement, standardization, and integration into practice.