Current opinion in pulmonary medicine
-
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. ⋯ 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.
-
Review
Role of biologics targeting type 2 airway inflammation in asthma: what have we learned so far?
Severe asthma is a heterogeneous syndrome that can be classified into distinct phenotypes and endotypes. In the type 2 (T2)-high endotype, multiple cytokines are produced that lead to eosinophilic inflammation. These cytokines and their receptors are targets for biologic therapies in patients with severe asthma who do not respond well to standard therapy with inhaled corticosteroids. ⋯ Biologics are emerging as a key component of severe asthma management. In patients with T2-high severe asthma, the addition of treatments targeting immunoglobulin E and IL-5 to standard therapy may lead to improvement in clinical outcomes. Other biologic therapies have shown promising preliminary results and need to be studied in further clinical trials. These biologic therapies in conjunction with biomarkers will lead to tailored therapy for asthma.