Evolving Concepts of Asthma

Abstract

Our understanding of asthma has evolved over time from a singular disease to a complex of various phenotypes, with varied natural histories, physiologies, and responses to treatment. Early therapies treated most patients with asthma similarly, with bronchodilators and corticosteroids, but these therapies had varying degrees of success. Similarly, despite initial studies that identified an underlying type 2 inflammation in the airways of patients with asthma, biologic therapies targeted toward these type 2 pathways were unsuccessful in all patients. These observations led to increased interest in phenotyping asthma. Clinical approaches, both biased and later unbiased/statistical approaches to large asthma patient cohorts, identified a variety of patient characteristics, but they also consistently identified the importance of age of onset of disease and the presence of eosinophils in determining clinically relevant phenotypes. These paralleled molecular approaches to phenotyping that developed an understanding that not all patients share a type 2 inflammatory pattern. Using biomarkers to select patients with type 2 inflammation, repeated trials of biologics directed toward type 2 cytokine pathways saw newfound success, confirming the importance of phenotyping in asthma. Further research is needed to clarify additional clinical and molecular phenotypes, validate predictive biomarkers, and identify new areas for possible interventions.

Keywords: asthma; biologic therapy; clustering; endotyping; phenotyping.

Figure 1.

A timeline showing major events in the understanding of asthma and phenotyping. The timeline is “semilogarithmic” in scale, emphasizing the growing amount of research in the field with time. Arrows below represent the emergence of various phenotype strategies. Background shows the overall changing interest in asthma phenotyping over time. CS = corticosteroids.

Figure 2.

An example of current asthma phenotypes as they relate to inflammatory type (type-2 high or low) and other variables. Note that many phenotypes overlap because currently there is no clear demarcation between these groupings. Patients may exhibit clinical or pathologic features of multiple groups, emphasizing the limitations in the current understanding of phenotypes and the ability to use them routinely in clinical practice at this current stage. CS = corticosteroids; GM-CSF = granulocyte–macrophage colony–stimulating factor.