What is it?
· Chronic inflammatory disorder of airways
Clinical
· Recurrent wheezing
· Cough
· Dyspnea
· Chest tightness
Causes?
· Repeated hypersensitivity
· Late-phase reaction
Results?
· Triad
o Intermittent / reversible airway obstruction
o Chronic bronchial inflammation
o Bronchial smooth muscle cell hypertrophy and hyperactivity
Epidemiology?
· 70% - extrinsic / atopic – due to IgE and Th2-mediated immune response to environmental antigens
· 30% - intrinsic/non-atopic – triggered by non-immune stimuli (eg. Aspirin, pulmonary infections
Pathogenesis?
· Genetic predisposition to type 1 hypersensitivity (atopy) and Bronchial hyper-responsiveness to variety of stimuli
· Role of Th2 helper – excessive response against environmental stimuli
o Cytokines – IL4 (IgE production), IL-5 (activation of eosinophils), IL-13(mucus production)
· Role of epithelial cells
o Produces chemokines -> attracts more Th2 and eosinophils + leukocytes à amplying inflammatory reaction.
· Structural changes in bronchial wall (airways remodeling) (ie bronchial smooth muscle hypertrophy)
o Thickening of basement membrane of bronchial epithelium
o Edema and inflammatory infiltrate in bronchial wall
o Increased size of mucosal glands
o Hypertrophy of bronchial muscle wall
· Mast cells – produce growth factors à stimulates SM proliferation
Types?
1) Atopic
· Most common
· Childhood onset
· Family hx – common
· Other atopic diseases (i.e rhinitis, eczema)
· Triggered by environmental antigens
· Skin test -> immediate wheal-flare reaction
· Process? Initial sensitization to inhaled antigens à thus stimulate Th2 cells à cytokines
· IgE production
· IgE binds to mucosal mast cells
· Results : immediate response + late phase reaction
· Subsequent exposure of IgE-coated mast cell to same antigen
· Crosslink and releasing of chemical mediators
· Results : opening of mucosal intercellular junctions à thus allowing penetration of antigen to more mucosal mast cells
· In additions : direct stimulation of subepithelial vagal (parasympathetic) receptors à provokes reflex bronchoconstriction
· Occurs within minutes after stimulation
· Called acute/immediate response (minutes)
o Bronchoconstriction
o Oedema (increased vascular permeability)
o Mucus secretion
· Late phase reaction (hours)
o Mast cells – cytokine release
o Thus, influx of other leukocytes + eosinophils
o Activation of eosinophils -> rich source of leukotrines C4
2) Nonatopic
· Family hx is uncommon
· Serum IgE normal
· No associated allergen
3) Drug-induced asthma
· Eg. Aspirin
· Presentation : recurrent rhinitis + nasal polyps, urticaria, bronchospasm
Status asthmaticus (prolonged severe asthma attack)