IM text book

• Asthma

  A heterogeneous disease characterized by chronic airway inflammation
• Asthma


  • Defined by history of respiratory symptoms (wheeze, shortness of breath, chest tightness, cough) that vary over time and in intensity
  • Associated with variable airflow limitation
• Chronic inflammation in asthma

  1. Leads to airway hyperresponsiveness

  2. Leads to recurrent symptoms (often worse at night or early in the morning)
• Variable airflow limitation in asthma

  • Caused by bronchial smooth muscle contraction
  • Caused by mucosal edema
  • Caused by formation of "mucus plugs"
• In some asthma patients, irreversible airflow limitation may be caused by airway remodeling
• Asthma phenotypes

  Different types of asthma
• Allergic asthma


  • Most common asthma phenotype
  • Allergen binds to IgE antibodies on mast cells
  • Leads to release of mediators (histamine, cysteinyl leukotrienes, prostaglandin D2, proteolytic enzymes)
  • Causes airway obstruction
• Allergic reaction in asthma

  1. Early phase: Allergen binding to IgE on mast cells

  2. Late phase: Mast cells, basophils, other cells release cytokines and chemokines

  3. Increases influx of inflammatory cells, particularly eosinophils, to airways
• Not all eosinophilic asthma is associated with allergen sensitization
• Type 2 asthma

  • Preferred term for eosinophilic asthma not associated with allergen sensitization
  • Cytokines causing persistent airway inflammation originate from Th-2 cells or innate lymphoid cells type 2
  • Characteristic cytokine profile (IL-4, IL-5, IL-13)
  • Influences IgE production, eosinophil and mast cell growth/differentiation/activation
• T2-high asthma

  Subset of asthmatic patients with type 2–high airway inflammation
• Allergic asthma

  • Begins in childhood
  • May coexist with other atopic diseases
  • Associated with family history of atopic diseases
  • Positive prick skin tests to inhaled allergens
  • Allergen-specific IgE antibodies in blood
• Patients with allergic asthma

  • Often have airway eosinophilia
  • Good response to inhaled corticosteroids (ICSs)
• T2-high inflammation

  Type 2 high inflammation
• Not all asthma patients have T2-high inflammation
• T2-low asthma

  Asthma with type 2 low inflammation
• The pathobiology of T2-low asthma is not as well understood
• T2-low asthma may be triggered by

  1. Immune process initiated by viral or bacterial infection

  2. Airway inflammatory cells are either neutrophils or very scarce (paucigranulocytic asthma)
• Airway histopathology is similar as in allergic asthma