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)