Severe asthma phenotypes and endotypes.

Current management of severe asthma relying either on guidelines (bulk approach) or on disease phenotypes (stratified approach) did not improve the burden of the disease. Several severe phenotypes are described: clinical, functional, morphological, inflammatory, molecular and microbiome-related. However, phenotypes do not necessarily relate to or give insights into the underlying pathogenetic mechanisms which are described by the disease endotypes. Based on the major immune-inflammatory pathway involved type-2 high, type-2 low and mixed endotypes are described for severe asthma, with several shared pathogenetic pathways such as genetic and epigenetic, metabolic, neurogenic and remodelling subtypes. The concept of multidimensional endotyping as un unbiased approach to severe asthma is discussed, together with new tools and targets facilitating the shift from the stratified to the precision medicine approach.