Emergence of Biomolecular Pathways to Define Novel Asthma Phenotypes. Type-2 Immunity and Beyond

Asthma is increasingly recognized as a heterogeneous entity, encompassing a variety of different subgroups, or phenotypes, which share clinical and inflammatory characteristics. However, it is only recently that molecular pathways have been both identified and successfully targeted in association with these clinical-inflammatory phenotypes. This integration of clinical-inflammatory and molecular pathways has enabled the broad differentiation of "asthma" into those with and without type-2 inflammation, on the basis of elevations in pathways downstream of type-2 cytokines, such as periostin, exhaled nitric oxide, and blood eosinophils. Although these rather general downstream biomarkers can identify patients more likely to respond to novel type 2-targeted therapies, they may have limited ability to determine which patients respond best to which type 2-targeted therapy, or even who will respond less than optimally, despite elevation in the biomarkers. In addition, new biomarkers and targets are required for the 50% of patients with asthma without elevations in these type-2 biomarkers. The path forward will require integrated 'omics approaches, development of more complex mouse models of asthma, as well as identification and validation of novel biomolecular pathways.