Pathophysiology

Pathophysiology of Asthma

Asthma is described in the current GINA guideline as a heterogeneous disease characterized by chronic airway inflammation and defined by history of respiratory symptoms that include wheeze, shortness of breath, chest tightness and cough of varying intensity over time in addition to variable expiratory airflow limitation. Symptoms and airflow limitations are a result of underlying pathophysiological characteristics (phenotypes) that drive disease progression. Until this is fully understood, phenotypes remain loosely linked to asthma pathology and clinical outcomes, though future data may reveal the details of this association.1

BREATH_Th2-Asthma-Phenotype

  • Asthma is characterized by inflammation3
  • Cytokines produced: IL-3, IL-4, IL-5, IL-13, IL-333
    • IL-3: Regulates eosinophil and basophil differentiation, migration and survival
    • IL-4: important for Th2 cell differentiation and IgE production
    • IL-5: Involved in eosinophil differentiation, maturation, recruitment and survival
    • IL-13: involved in lung inflammation, mucus hypersectretion, subepithelial fibrosis and eotaxin production
    • IL-33: IL-33 receptor (ST2) is a marker for Th2, activates Th2 cells
  • IL-25 and thymic stromal lymphopoietin (TSLP): potential to induce features of Th2-type response such as eosinophilia and the production of IL-4, IL-5, IL-13 and IgE Ab
  • Allergen challenge results in influx of activated Th2 cells into the airway in addition to an increase of Th2 cytokines and recruitment of eosinophils3,4
    • Number of Th2 cells in airway correlates with disease severity
  • Reduction of specific Th2 responses can treat disease without causing generalized immmunosupression

 

Non-Th2 Asthma Phenotype2

References:

  1. Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA). Updated 2020. Available: ginasthma.org.
  2. Wenzel SE. Nat Med. 2012;18:715-725.
  3. Lloyd CM, et al. Nat Rev Immunol. 2010;10:838-848.
  4. Bosnjak B, et al. Respiratory Research. 2011;12:114.