Asthma (12/6/16) - Martin

Question 1

What is asthma?

When does it present?

Answer 1

Reversible airway bronchoconstriction, most often due to allergic stimuli

Presents in childhood; often associated w allergic rhinitis, eczema, and family hx of atopic rxns

Question 2

Pathogenesis (Type I Hypersensitivity)

Answer 2

1. Allergens induce T_H2 phenotype in CD4+ T cells of genetically susceptible individuals
2. T_H2 cells secrete:
   
   1. IL-4 (mediates plasma cell class switch to IgE)
   2. IL-5 (attracts eosinophils)
   3. IL-10 (stimulates T_H2 cells and inhibits T_H1)
3. Re-exposure to allergens → IgE-mediated activation of mast cells
   
   1. Early phase rxn:
      
      1. Release of preformed histamine granules
      2. Generation of leukotrienes C4, D4, and E4 → bronchoconstriction, inflammation, edema
   2. Late phase rxn: Inflammation, especially major basic protein derived from EOSINOPHILS, damages cells → perpetuates bronchoconstriction

Question 3

Clinical features

Answer 3

Episodic

Related to allergen exposure

• Dyspnea and wheezing
• Tachypnea
• Smooth muscle hypertrophy
• Hypoxemia
• Productive cough, classically w spiral-shaped mucus plugs (Curschmann spirals) and eosinophil-derived crystals (Charcot-Leyden crystals)
• Severe, unrelenting attack → status asthmaticus and death (bronchoconstriction will not relieve itself)

Question 4

Asthma may also arise from nonallergic causes (non-atopic asthma)

Answer 4

• Exercise
• Viral infection
• Aspirin (e.g., aspirin intolerant asthma) → nasal polyps in adults!
• Occupational exposures

Question 5

Underlying problem: Inflammation or bronchodilation?

Answer 5

Asthma is an inflammatory illness associated with bronchial hyperreactivity that results in bronchospasm.

Question 6

Why is it advantageous to apply drugs to the lungs topically?

Answer 6

Pathophysiology of asthma involves respiratory tract alone.

AEROSOL:

• Produces high local concentrations
• Minimizes systemic delivery

Aerosol devices:

• Metered-dose inhalers (MDIs): fluid/solid
• Nebulizers: mist
• Dry powder inhalers (DPIs): powder

Question 7

Even under ideal circumstances, only 2-10% of aerosolized drug is deposited in the lungs, with the remainder being swallowed.

How to create aerosolized drug to minimize systemic effects? (2)

Answer 7

1. Should be poorly absorbed from GI system or
2. Rapidly inactivated via first-pass hepatic metabolism
   
   1. In this case, you WANT first-pass

Question 8

General order of drugs used in treatment of asthma

Answer 8

1. Bronchodilators - relieve acute symptoms (immediate attack)
2. Anti-inflammatory agents - used to control or prevent symptoms (prevent exacerbation)