Pathogenesis of asthma

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Pathogenesis of asthma

• Prof John J. OLeary

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Lung
Type I pneumocyte
Type I pneumocyte
Alveolar space
Capillary lumen
Type II pneumocyte
Endothelium
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Learning objectives

• Understand the patho-physiology of asthma
• Know what tests need to be done
• Asthma therapeutics
• Future molecular approaches to asthma

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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

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Common triggers for asthma
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Proposed mechanism for antigen mast cell,
eosinophil interaction in asthma
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Atopic asthma
Epithelial cell injury
Allergen
IgE
Mucus secretion
Muscle contraction
Mucus secretion
Mast cell
Muscle contraction
Release of inflammatory mediators
Recruitment of leukocytes
Acute phase
Late-phase
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Exercise induced asthma
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Disease characteristics
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Disease pathology
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Epithelial remodeling
Macrophages
Histamine Leucotrienes Prostaglandins
Mast cells
Eosinophils
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Eosinophil granules release airway remodeling
factors
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Epithelial remodeling
CONTROL

• Epithelium is damaged
• New blood vessels
• New muscle
• New mucosal cells
• Collagen deposition

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Epithelial remodeling Apoptosis
Control
Asthma patient
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Loss of columnar cells
Normal
Asthma patient
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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
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Tightness of chest, breathing trouble
BRONCHIAL CONSTRICTION Histamine, prostaglandins
and leucotrines
INFLAMMATION
AIRWAY REMODELLING
HYPERESPONSIVE
EXCESS MUCOUS SECRETION
Coughing and wheezing
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Clinical presentation
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Investigating asthma
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FEV1 in men and women
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Investigating asthma
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Investigating asthma prognostic indices
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Investigating asthma
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Treating asthma
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Treating asthma adverse effects
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Treating asthma other therapeutic approaches
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Risk factors for fatal/near-fatal asthma
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Molecular biological approaches in asthma