Bronchial Asthma

Bronchial Asthma

1. Episodic & reversible airway disease

2. Primarily targets the bronchi & its subdivisions & nonrespiratory bronchioles

3. Extrinsic Asthma

   • Pathogenesis
     • Type 1 HSR with exposure to extrinsic allergen
     • Initial sensitization to an inhaled allergen
       • Stimulate induction of CD4 TH2 >> release IL-4 & IL-5
         • IL4 stimulates isotype switching to IgE production
         • IL 5 stimulates production and activation of eosinophils
     • Inhaled Antigens cross link IgE antibodies on mast cells on mucosal surfaces
       • Release of histamine & other performed mediators
       • Function of Mediators : stimulate BRONCHOCONSTRICTION, Mucus Production, Influx of Leukocytes
     • Late phase reaction ( 4-8 h)
       • Eotaxin is produced
         • Chemotactic and activator for eosinophils
       • Eosinophils release major basic protein and cationic protein
         • Damage epithelial cells and produce airway constriction
     • Other mediators involved:
       • (1) Leukotrienes LTC-D-E4 causes prolonged bronchoconstriction.
       • (2) Acetylcholine causes airway muscle contraction.
     • Histologic Changes in Bronchi
       • (1) Thickening of the basement membrane
       • (2) Edema and a mixed inflammatory infiltrate
       • (3) Hypertrophy of submucosal glands
       • (4) Hypertrophy/hyperplasia of smooth muscle cells
     • Histologic Changes in Bronchioles
       • (1) Formation of spiral-shaped mucus plugs
         • (a) Contain shed epithelial cells called Curschmann spirals
         • (b) Pathologic effect of MBP and cationic protein
       • (2) Crystalline granules in eosinophils coalesce to form Charcot-Leyden crystals.
       • (3) Patchy loss of epithelial cells, goblet cell metaplasia
       • (4) Thick basement membrane
       • (5) Smooth muscle cell hypertrophy and hyperplasia
   • Clinical Findings
     • Episodic expiratory wheezing
     • Nocturnal cough
     • Increased anteroposterior diameter << air trapping & increased residual volume
   • Lab Findings:
     • Initially develop respiratory alkalosis; normal pH or respiratory acidosis indicates need for intubation
     • FEV1 is best measure of severity
     • Eosinophilia, positive skin tests for allergens

4. Intrinsic Asthma

   • Nonimmune
   • Causes
     • Virus induced respiratory infection ex. rhinovirus, parainfluenza, respiratory syncytial viruses
     • Air Pollutant
     • Aspirin or NSAID sensitivity
       • COX inhibition leaves lipoxygenase pathway open for productionn of leukotrienes
     • Stress, exercise, cigarette smoke