“An impressive amount of progress has been made in identifying the molecular pathways that mediate type 2-high asthma, which has culminated in the introduction into clinical practice of neutralizing antibodies that specifically target IgE, type 2 cytokines (IL-4, IL-5, IL-13), and the airway epithelial cell-derived cytokine, thymic stromal lymphopoietin (TSLP),” Commentary authors write. “These biologic therapies reduce asthma exacerbations, allow reductions in corticosteroid requirements, and improve lung function when administered to patients with type 2-high asthma.”
Patients with type 2-low asthma — those having low blood eosinophil counts and low exhaled levels of nitric oxide (Feno) and disease that is not clinically allergen-driven — “tend to be less responsive to corticosteroids and are characterized by neutrophilic airway inflammation or as being pauci-granulocytic (with neither neutrophilic nor eosinophilic airway inflammation),” the authors write. “The molecular pathways that mediate type 2-low asthma are less well-defined than for type 2-high asthma. Tezepelumab, a neutralizing antibody directed against TSLP, which currently is available for clinical use, is a biologic agent that reduces exacerbations in patients with severe asthmatics with either type-2 high or type 2-low disease, which includes individuals with blood eosinophil counts < 150 cells/mL or Feno levels < 25 parts per billion. Potential mechanisms by which TSLP neutralization may be beneficial for the treatment of patients with type 2-low asthma include effects on neutrophils, mast cells, smooth muscle cells, and fibroblasts.…”