Defining severe asthma and differentiating severe from milder disease

2 3 9 4 jci.org Volume 126 Number 7 July 2016 A brief overview Asthma identifies a spectrum of respiratory-related symptoms, typically with a link to reversible airflow limitation. Like the terms arthritis or anemia, the term asthma does not identify any specific underlying pathobiology, but is a broad, umbrella-like term that covers multiple groupings of patient characteristics or phenotypes (1–3). While the term asthma has been traditionally used to describe a childhood onset disease associated with atopic/allergic responses, asthma can develop later in life, with minimal link to allergy. Although mild to severe disease has been identified across the spectrum of asthma, many studies now show that “severe asthma” is not a phenotype, but rather a description of a group of patients with high medical needs, whose pathobiologic and clinical characteristics vary widely (1, 4–8). This heterogeneity has made the study of the underlying pathobiologies of severe asthma problematic. Therefore, to move the understanding of severe asthma forward, several factors deserve attention, including (a) a unified clinical definition of the umbrella-term asthma, (b) biased and unbiased approaches for the identification of clinical and (ideally) matched molecular phenotypes, (c) animal models to address the importance of specific molecular pathways, and (d) targeted treatment approaches in humans that confirm the relevance of particular molecular pathways to defined clinical molecular phenotypes. Linking these steps should enable identification of precisely treatable endotypes of severe asthma (2, 7, 9).