Fiche de révision : Asthma Pathophysiology

📋 Course Outline

1. Asthma Definition
2. Asthma Etiology and Triggers
3. ASA Sensitivity Pathway
4. Allergen Recognition and Th2 Response
5. IgE and Mast Cell Activation
6. Eosinophils and Airway Effects

📖 1. Asthma Definition

🔑 Key Concepts & Definitions

• Asthma : A chronic inflammatory condition of the respiratory mucosa characterized by narrowing of the respiratory passageways that causes attacks of impaired breathing.

📖 2. Asthma Etiology and Triggers

🔑 Key Concepts & Definitions

• Hygiene hypothesis : Proposes that reduced exposure to different pathogens can increase susceptibility to asthma because of alterations in leukocyte maturation.

📝 Essential Points

• The atopic triad consists of asthma, atopic dermatitis (eczema), and atopic rhinitis.

• Samter's triad consists of asthma, nasal polyps, and acetylsalicylic acid (ASA) sensitivity.

• Other asthma triggers listed in the course are dust, smoke, pollution, pet dander or hair, cockroaches, cold weather, exercise, viral upper respiratory tract infections, emotional stress, and beta blockers.

📖 3. ASA Sensitivity Pathway

★ Must-know

• Arachidonic acid can be metabolized by cyclooxygenase (COX) to form prostaglandins PGE2, PGI2, and PGF2, or by lipoxygenase (LPO) to form leukotrienes.

• In some individuals with ASA sensitivity, inhibition of the COX pathway increases LPO activity and produces large quantities of leukotrienes.

Further detail

• Lิวkotriene B4 acts as a chemotactic agent, whereas leukotrienes C4, D4, and E4 cause bronchospasms.

• The excess leukotrienes associated with ASA sensitivity cause bronchospasms, increased vascular permeability, and increased mucus production.

💡 Memory Hook

COX down, LPO up

📖 4. Allergen Recognition and Th2 Response

📝 Essential Points

• Dendritic cells or macrophages recognize a specific allergen and internalize it by phagocytosis or endocytosis, inducing MHC-II activation and allergen expression on MHC-II.

• Antigen-presenting cells present the allergen to Th2 cells, whose T-cell receptors react with the antigen and trigger release of IL-4 and IL-5.

• IL-4 released by Th2 cells activates plasma cells and induces production of allergen-specific IgE antibodies.

💡 Memory Hook

APC → MHC-II → Th2 → IL-4/IL-5

📖 5. IgE and Mast Cell Activation

📝 Essential Points

• Allergen-specific IgE antibodies bind to FcεR1 receptors on mast cell membranes, causing mast cell degranulation.

• Mast cell degranulation causes massive production and release of histamines and leukotrienes.

💡 Memory Hook

IL-4 → IgE → FcεR1 → degranulation

📖 6. Eosinophils and Airway Effects

★ Must-know

• IL-5 released by Th2 cells activates eosinophils, inducing them to release leukotrienes and proteases.

• Histamines and leukotrienes induce bronchoconstriction through contraction of bronchial smooth muscle, mucus buildup from inflammatory-cell infiltration, mucosal inflammation with fluid and inflammatory cells, and increased vascular permeability.

Further detail

• Chronically released eosinophil proteases cause tissue damage to the respiratory tract.

📊 Synthesis Tables

Asthma-Associated Triads