Asthma Phenotypes and Endotypes: Implications for Personalised Therapy

Abstract

Asthma is increasingly recognised as a heterogeneous group of diseases with similar clinical presentations rather than a singular disease entity. Asthma was historically categorised by clinical symptoms; however, newer methods of subgrouping, describing and categorising the disease have sub-defined asthma. These sub-definitions are intermittently called phenotypes or endotypes, but the real meanings of these words are poorly understood. Novel treatments are currently and increasingly available, partly in the monoclonal antibody environment, and also some physical therapies (bronchial thermoplasty), but additionally small molecules are not far away from clinical practice. Understanding the disease pathogenesis and the mechanism of action more completely may enable identification of treatable traits, biomarkers, mediators and modifiable therapeutic targets. However, there remains a danger that clinicians become preoccupied with the concept of endotypes and biomarkers, ignoring therapies that are hugely effective but have no companion biomarker. This review discusses our understanding of the concept of phenotypes and endotypes in appreciating and managing the heterogeneous condition that is asthma. We consider the role of functional imaging, physiology, blood-, sputum- and breath-based biomarkers and clinical manifestations that could be used to produce a personalised asthma profile, with implications on prognosis, pathophysiology and most importantly specific therapeutic responses. With the advent of increasing numbers of biological therapies and other interventional options such as bronchial thermoplasty, the importance of targeting expensive therapies to patients with the best chance of clinical response has huge health economic importance.