Molecular Markers of Phenotypes and Endotypes
Ioana Agache
A phenotype covers the visible properties of a disease. Although clinically relevant it does not
reflect the underlying pathophyiologic mechanisms, which are addressed by the endotypes.
Accurate endotyping of asthma starts with the identification of corresponding molecular
biomarkers for each pathogenic mechanism operating within an asthma phenotype or
subphenotype. Various biomarkers are described for eosinophilic inflammation, Th2
profile/allergic inflammation, intrinsic/non-atopic asthma, neutrophilic inflammation,
neurogenic inflammation, immune regulation in asthma, innate immunity, resolution of
inflammation, airway remodelling, airway hyperreactivity, susceptibility to asthma
exacerbations, age-related differences in asthma, sex-related differences in asthma, severe
asthma, decreased response to corticosteroids or beta2 agonists. The relevance of each
biomarker should be supported by the validity and plausibility of the mechanism involved and
should be tested in experimental models and consequent intervention trials. A good example
of valid biomarkers would be their capability to predict response to targeted treatment in
asthma (sputum eosinophils and anti IL-5, periostin and anti IL-13). Furthermore the
biomarkers related to an endotype should prove stable over time or with a predictable
variation pattern and should be replicated across populations with different genetic
background.