The Advance of Personalized and Stratified Therapies in Bronchial Asthma: Phenotypes – Endotypes – Biomarkers

摘要

Bronchial asthma (BA) is a chronic inflammatory condition with increasing incidence and prevalence worldwide. BA is currently the most prevalent chronic disease in pediatric patients. The majority of BA patients are therapeutically well controlled with guideline based anti-inflammatory therapies; however, there is also a clinically recognized proportion of patients who do not benefit from currently available medication for several reasons. This is the starting point for further investigation into the complexity of the inflammatory phenotype of BA. Recently, the heterogeneity in terms of cellular and molecular pathways underlying BA has been recognized and established. These different pathogenic mechanisms are defined as ‘endotypes’. The best studied endotype so far is the association with T-helper type 2 (TH2) cell eosinophilic airway inflammation. Recently, a number of different therapeutic strategies have been clinically explored which target certain mediators of this pathway, including the interleukins IL-4, IL-5 and IL-13. It is now clear that patients with the TH2-endotype largely benefit from novel biologicals in this area. However, the challenge for diagnostics is to identify patients exhibiting this endotype, and this is the starting point for the search for new biomarkers. One biomarker that has recently been selected based on differential gene expression analysis, and which seems to be strongly associated with the TH2 endotype, is periostin. In this article we will provide a state of the art update on the definition of clinical phenotypes, pathogenetic endotypes and biomarker development for improving BA treatment.