endotypes

An endotype is a disease subtype defined by distinct pathobiological mechanisms that drive disease development and progression. This concept contrasts with phenotype, which refers to observable clinical features or presentation without specifying underlying mechanism. Endotypes are used to explain why patients with the same clinical diagnosis can respond differently to treatments.

In modern medicine, endotyping supports precision medicine by linking biomarkers and molecular pathways to therapeutic responses. Identification usually relies on molecular, cellular, or imaging data, such as biomarker signatures, gene expression, or inflammatory patterns in tissues or blood.

Asthma is a frequently cited example, with endotypes such as Type 2 (T2) high, characterized by eosinophilic inflammation driven by IL-4, IL-5, and IL-13, and often responsive to corticosteroids and to biologic therapies targeting these pathways. Non–Type 2 asthma includes neutrophilic or paucigranulocytic endotypes and can be less responsive to standard treatments. Other diseases where endotypes are used include chronic obstructive pulmonary disease, allergic rhinitis, and several cancers, where molecular drivers define subtypes.

Endotyping relies on biomarkers and molecular data such as blood eosinophils, fractions of exhaled nitric oxide (FeNO), gene expression, proteomics, and metabolomics, sometimes integrated with imaging and clinical data.

Limitations include overlap among endotypes, dynamic changes over time, and the absence of universally validated biomarkers for all diseases. Practical challenges include access to testing and cost.

Clinical impact: Endotyping informs precision medicine by guiding therapy choices, prognosis, and monitoring, including the use of targeted biologic agents in asthma and other conditions.