Transcript Pathogenesis-of-asthma-14

Pathogenesis of asthma
Prof John J. O’Leary
Lung
Type I
pneumocyte
Type I
pneumocyte
Alveolar
space
Capillary
lumen
Type II
pneumocyte
Endothelium
Learning objectives
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Understand the patho-physiology of asthma
Know what tests need to be done
Asthma therapeutics
Future molecular approaches to asthma
Bronchial Asthma
• Chronic inflammatory disorder of the airways
resulting in contraction of bronchial muscle
• Types
– Extrinsic (atopic, allergic)
• Allergens: food, pollen, dust, etc.
– Intrinsic (non-atopic)
• Initiated by infections, drugs, pollutants, chemical irritants
Common triggers for asthma
Proposed mechanism for
antigen –mast cell, eosinophil
interaction in asthma
Atopic asthma
Allergen
IgE
Mucus
secretion
Mast cell
Epithelial cell
injury
Muscle
contraction
Mucus
secretio
n
Muscle contraction
Recruitment of
leukocytes
Release of
inflammatory
mediators
Acute phase
Late-phase
Exercise induced asthma
Asthma Prevalence: CDC
Disease characteristics
Disease pathology
Epithelial
remodeling
Macrophages
Histamine
Leucotrienes Mast cells
Prostaglandins
Th cells
Smooth muscle constriction
Th cells
Eosinophils
Eosinophil granules release airway
remodeling factors
Epithelial remodeling
• Epithelium is damaged
• New blood vessels
• New muscle
• New mucosal cells
• Collagen deposition
Epithelial remodeling
Apoptosis
Control
Asthma patient
Loss of columnar cells
Normal
Asthma
patient
PATHOLOGICAL BASIS
Hallmark of asthma
Inflammation
Tightening of airway muscles
Mucus secretion
Hyper responsiveness
Airway remodeling
Asthma -
chronic inflammatory disease
reversible airway obstruction
airway remodeling
Tightness of chest, breathing trouble
BRONCHIAL
CONSTRICTION
Histamine, prostaglandins
and leucotrines
INFLAMMATION
AIRWAY
REMODELLING
HYPERESPONSIVE
EXCESS MUCOUS
SECRETION
Coughing and wheezing
Clinical presentation
Investigating asthma
FEV1 in men and women
Investigating asthma
Investigating asthma:
prognostic indices
Investigating asthma
Treating asthma
Treating asthma:
adverse effects
Treating asthma:
other therapeutic approaches
Risk factors for fatal/near-fatal
asthma
Molecular biological approaches in
asthma