What is the Underlying Pathophysiology of Extrinsic Asthma (Allergic Asthma, Type I Hypersensitivity Reaction)?

Overview:

• Asthma involves airway inflammation and bronchoconstriction triggered by allergens.
• The process is similar to allergic reactions described in lessons on allergies.

Initial Exposure to Allergen:

• The allergen (e.g., dust or pollen) is inhaled.
• In a hypersensitive individual, the immune system inappropriately recognizes the harmless allergen as harmful.
• Macrophages present the allergen to helper T cells.
• Helper T cells activate B cells, leading to proliferation and differentiation into plasma cells.

Antibody Production:

• IgE antibodies are produced by plasma cells.
• These IgE antibodies are different from IgG; IgG fights bacteria, while IgE is involved in allergy responses.
• IgE binds to receptors on mast cells (tissue-resident) and basophils (bloodstream).

Sensitization:

• Upon re-exposure to the same allergen, mast cells and basophils—now sensitized—are activated.
• They release histamine and other mediators.

Effects of Histamine Release:

• Vasodilation and increased capillary permeability → edema, redness, and swelling in the respiratory mucosa.
• Bronchoconstriction: smooth muscles in bronchioles constrict, narrowing airways.
• Increased mucus secretion: hypersecretion and mucus plugs develop, obstructing airflow.

Resulting Pathophysiological Changes:

• Airway narrowing leads to difficulty breathing.
• Mucus plugs further block gas exchange surfaces.
• Edema and mucus accumulation cause partial airway obstruction, leading to air trapping and hyper-inflation of alveoli.
• Narrowed airways and mucus plugs cause partial obstruction, reducing airflow and gas exchange.

Clinical Manifestations:

• Dyspnea (shortness of breath).
• Cough, often as a reflex to clear mucus.
• Wheezing due to bronchoconstriction.
• Hypoxia due to impaired oxygen exchange.
• Anxiety and confusion from low oxygen levels.
• Severe attacks can cause cyanosis and respiratory distress.

Progression Over Time:

• Persistent or recurrent attacks cause:
  • Chronic inflammation.
  • Recruitment of leukocytes: basophils, neutrophils, eosinophils.
  • Release of pro-inflammatory mediators such as leukotrienes, which sustain vasodilation and bronchoconstriction.
  • Epithelial damage, mucosal swelling, and mucus hypersecretion.
• Air trapping occurs because constricted bronchioles prevent complete exhalation, leading to hyperinflation (lungs behave as if breathing through a straw).

Advanced Pathology:

• Progressive obstruction causes atelectasis (lung collapse) due to alveolar non-aeration.
• Reflex vasoconstriction occurs in pulmonary arteries when oxygen sensing indicates low oxygen levels.
  • Pulmonary arteries constrict in poorly ventilated areas, leading to pulmonary hypertension.
  • Elevated pulmonary vascular resistance strains the right ventricle, potentially leading to right-sided heart failure (cor pulmonale) over time.

Chronic Effects:

• Repeated attacks cause damage to elastic fibers and alveolar wall structures.
• This results in less elasticity, fibrosis, and structural remodeling.
• Over time, persistent pulmonary hypertension can damage the heart.

Importance of Attack Prevention:

• Limiting the frequency and severity of attacks prevents progressive lung damage, elasticity loss, and pulmonary hypertension.
• Management aims to reduce inflammation, prevent bronchospasm, and avoid triggers.

Summary:  

Extrinsic asthma involves hypersensitivity reactions triggered by inhaled allergens, leading to airway inflammation, bronchoconstriction, mucus hypersecretion, and air trapping. Chronic or severe episodes can cause structural lung damage, airway remodeling (e.g., mucus gland proliferation and smooth muscle hyperplasia and hypertrophy), and secondary heart failure due to pulmonary hypertension. Proper control and avoidance of triggers are essential to prevent long-term damage.