T2-low Asthma

Abstract

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.