The document discusses the pathophysiology of airway inflammation in asthma. It describes how allergen exposure leads to production of IgE antibodies and activation of mast cells and eosinophils, causing bronchoconstriction and recruitment of inflammatory cells. Chronic inflammation can lead to structural changes in the airways known as remodeling through processes like increased airway smooth muscle mass and fibrosis. Modulatory factors include genetic predisposition as well as environmental exposures.

1. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
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by Dr. Eashan Srivastava

2. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
AIRWAY INFLAMMATION
● Involves the cells that play prominent roles in the allergic response
● Allergen exposure via inhalation
● Production of specific IgE antibodies
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by Dr. Eashan Srivastava

3. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
○ Overexpression of Th2 type T cell responses
● IgE antibodies bind to high-affinity receptors on mast cells
● When an allergen is subsequently inhaled
○ Cross links allergen-specific IgE antibodies on the mast cell surface
○ Degranulation and mediator release
● Early & Late phase reactions
○ Allergen inhalation by a sensitized individual
○ Within minutes
■ Bronchoconstriction
■ Release of mast cell mediators including histamine, prostaglandin D2,
and leukotrienes (LTC4, D4, and E4)
○ Hours later
■ Bronchoconstriction
■ Recruitment of inflammatory
● Eosinophil
● Basophil
● Neutrophil,
● T-cells
● EOSINOPHILS
● Most characteristic cell in asthma
● Produces several mediators
○ Major basic protein
○ Eosinophil-derived neurotoxin
○ Eosinophil peroxidase
○ Eosinophil cationic protein
○ Can damage airway epithelium
● Recruited or activated by IL 5
● Mast cells
○ Producing bronchoconstricting mediators
■ Histamine
■ Prostaglandins
■ Leukotrienes
■ TNF-alpha= Recruitment and activation of inflammatory cells
- Created with love
by Dr. Eashan Srivastava

4. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
● Th2 lymphocytes
○ Produce IL-3, IL-4, IL-5, IL-13, and GM-CSF
○ IL-3
■ Survival factor for eosinophils and basophils
○ IL-4
■ Differentiation of uncommitted T cells into Th2 cells
■ IgE class switch
■ VCAM-1 expression that mediates eosinophil, basophil recruitment
○ IL-5
■ Increased eosinophil production and survival
○ IL-13
■ Mucous gland hyperplasia
■ Airway fibrosis
■ Remodeling
EPITHELIAL-MESENCHYMAL CONTRIBUTION
● "epithelial-mesenchymal trophic unit" plays a central role in inflammation and remodeling
● According to this theory, structural cells, particularly bronchial epithelial cells, fibroblasts,
smooth muscle, and vascular endothelial cells, elaborate mediators and cytokines that
contribute to inflammation and/or airway remodeling
PHYSIOLOGY OF AIRFLOW OBSTRUCTION
● Smooth muscle
○ Contraction of airway smooth muscle accounts for airflow limitation
○ Mediated by
■ Reflex neural mechanisms
■ Mediators
● Leukotrienes C4, D4, and E4
● Histamine
● Prostaglandins
○ Bronchial thermoplasty
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by Dr. Eashan Srivastava

5. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
■ Technique that applies radiofrequency waves to the airways during
bronchoscopy to decrease large airway smooth muscle mass
■ Support a central role for ASM in large airways in the pathogenesis
● Bronchial hyperresponsiveness
○ Reversible airflow obstruction
○ Exaggerated constrictor response to allergens
○ Calculated by the dose response to pharmacologic agents
■ Dose of Methacholine or histamine causing a 20% fall in FEV​1
○ Mechanism
■ Altered smooth muscle function or mass
■ Inflammatory mediators
■ Loss of airway-parenchymal interdependence
■ Loss of a bronchodilating effect of deep breaths
■ Enhanced sensitivity of neural pathways
AIRWAY REMODELING
● Patients may have irreversible airflow obstruction
● Airway remodeling refers to structural changes in the airways that may cause irreversible
airflow limitation, superimposed on the effects of inflammation and smooth muscle
contraction described above
● Histopathology
○ Loss of the normal pseudostratified structure of airway epithelium
○ Increase in the proportion of mucous-producing goblet cells
○ Fibrosis
○ Increased numbers of myofibroblasts
○ Increased airway smooth muscle mass
○ Increased extracellular matrix
MODULATORY FACTORS
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by Dr. Eashan Srivastava

6. We are all born ignorant, but one must work hard to remain stupid.
-Benjamin Franklin
Genetic factors
Environmental factors
● Air pollution
● Allergens (eg, dust mite, occupational allergens)
● Cigarette smoke
● Endotoxin
Infectious agents
Both bacterial and viral respiratory tract infections have been associated with increased risk of
asthma
- Created with love
by Dr. Eashan Srivastava