PURPOSE OF REVIEW

Asthma is a heterogeneous disease not only on a clinical but also on a mechanistic level. For a long time, the molecular mechanisms of asthma were considered to be driven by type 2 helper T cells (Th2) and eosinophilic airway inflammation; however, extensive research has revealed that T2-low subtypes that differ from the dominant T2 paradigm are also common.

RECENT FINDINGS

Research into asthma pathways has led to the recognition that some asthma phenotypes show absence of T2 inflammation or alternate between T2 and non-T2 responses. Moreover, numerous immune response modifiers that block key-molecules such as interleukin (IL)-5, IL-13, and immunoglobulin E (IgE) have been identified. Along the way, these studies pointed that T2-low inflammation may also be responsible for lack of responsiveness to current treatment regimes.

SUMMARY

Asthma pathogenesis is characterized by two major endotypes, a T2-high featuring increased eosinophilic airway inflammation, and a T2-low endotype presenting with either neutrophilic or paucigranulocytic airway inflammation and showing greater resistance to steroids. This clearly presents an unmet therapeutic challenge. A precise definition and characterization of the mechanisms that drive this T2-low inflammatory response in each patient phenotype is necessary to help identify novel drug targets and design more effective and targeted treatments.