Asthma is a chronic inflammatory disease of the airways characterized by wheezing, shortness of breath, and coughing. It has several subtypes including atopic asthma triggered by environmental allergens in childhood, non-atopic asthma without sensitization, and drug or occupational asthma caused by specific exposures. The pathogenesis involves a Th2 immune response leading to IgE production, eosinophil recruitment, and airway inflammation. Early phase responses include bronchoconstriction and increased mucus while late phases involve leukocyte recruitment. Genetic and environmental factors contribute to susceptibility. Histologically, asthmatic airways show thickening, inflammation, fibrosis and increased glands.

1. Asthma - Pathogenesis
Dr Tamil Nila
II year postgraduate
Department of Pathology

2. What is Asthma?
• Heterogenous disease
• Chronic airway inflammation
• Expiratory airflow obstruction
• Symptoms
• Wheezing
• Shortness of breath
• Chest tightness
• cough

3. Major subtypes
• Atopic Asthma
• Type 1 hypersensitivity
• Childhood
• Environmental allergens
• Positive family history
• High total serum IgE levels
• Serum radioallergosorbent tests
• Non Atopic asthma
• No evidence of sensitization
• Less common family history
• Associated with
• Viral respiratory infections
• Air pollutants
• Cold

4. Major subtypes
• Drug – Induced asthma
• Aspirin sensitive asthma
• NSAIDs
• Associated with utricaria
• Occupational asthma
• Fumes
• Dusts
• Chemicals
• Even minute quantities are
sufficient
• Repeated exposure
Inhibition of COX
Arachidonic acid not
metobolised
Less Prostaglandin E2

5. Pathogenesis
• Th2 responses, IgE and Inflammation
• Genetic susceptibility
• Environmental factors

6. Th2 responses, IgE and Inflammation
Th2 cells
IL -4
Ig E
production
IL – 5
Eosinophil
recruitment
IL – 13
Endobronchial
Secretions
Th 17
IL – 17
Neutrophil
recruitment

7. Triggering of Asthma

8. Early Phase
Bronchoconstriction
Increased mucus production
Vasodilation
Vascular permeability

9. Late Phase
Recruitment of Leucocytes
- Eosinophils
- Neutrophils
- More T cells

10. Mediators
Definite
Leucotrienes
C4, D4 & E4
Acetylcholi
ne
IL -5
Galectin 10
Minor
role
Histamine
Prostagland
in D2
PAF
Others
IL – 4
IL – 13
TNF

11. Genetic susceptibility
• Chromosome 5q
• Gene cluster encoding for IL 3, IL 4, IL 5, IL 9, IL 13 & IL 4 receptor
• Class II HLA alleles
• Genes encoding
• IL 33
• Thymic stromal lymphoprotein

12. Environmental factors
Industrial
Air
pollutants
Hygiene
hypothesis

13. Exaggerated response
Airway Inflammation
Airway Dysfunction
Airway remodelling

14. Normal vs Asthmatic Airway

15. Gross
• Hyperinflated lungs
• Occlusion of bronchi by thick,
tenacious mucus plugs

16. Microscopy
• Airway wall thickening
• Eosinophilic inflammation
• Goblet cell hyperplasia
• Muscle hypertrophy
• Sub basement membrane
fibrosis
• Increased vascularity
• Increased size of submucosal
glands

17. BAL Wash findings
Curschmann spirals Charcot leyden crystals

18. References
• Robbins and Cotran pathologic basis of disease
• Autopsy pathology – A manual and atlas, Andrew J. Connolly
• Comprehensive Cytology, Marluce Bibbo