Evolving Concept of Severe Asthma: Transition From Diagnosis to Treatable Traits

Abstract

In recent decades, the concept of severe asthma has evolved from an umbrella term encompassing patients with high-intensity treatment needs to a clinical syndrome with heterogeneous, albeit distinct, pathophysiological processes. Biased and unbiased cluster approaches have been used to identify several clinical phenotypes. In parallel, cellular and molecular approaches allow for the development of biological therapies, especially targeting type 2 (T2) cytokine pathways. Although T2-biologics have significantly improved clinical outcomes for patients with severe asthma in real-world practice, questions on the proper use of biologics remain open. Furthermore, a subset of severe asthma patients remains poorly controlled. The unmet needs require a new approach. The "treatable traits" concept has been suggested to address a diversity of pathophysiological factors in severe asthma and overcome the limitations of existing treatment strategies. With a tailored therapy that targets the treatable traits in individual patients, better personalized medical care and outcomes should be achieved.

Keywords: Asthma; biological products; biologics; cytokines; endophenotypes; omics; outcomes; precision medicine.

Fig. 1. Evolving concept in asthma management during the last few decades. The concept has evolved to address major unmet needs. The introduction of ICS as the maintenance therapy was the first breakthrough in asthma management, which considerably reduced asthma-related hospitalization and mortality. The subsequent development of LABAs and LAMAs further reduced asthma symptoms and exacerbation as well as improved lung functions. T2-associated biological therapies are the most recent breakthrough in the management of severe asthma. However, several clinical needs remain unmet. Treatable traits are emerging as a concept to further address patient heterogeneity in severe asthma.

ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; OCS, oral corticosteroid; T2, type 2.

Fig. 2. Endotype, phenotype, and significant treatable traits from respiratory, extra-respiratory, and behavioral domains in severe asthma. Specific investigations and treatments are undertaken for each trait in individuals, allowing for precision medicine in patients with severe asthma.

T2, type 2.