What Actually Happens in the Airways During Asthma? 🫁

🔬 A deep dive into the pathophysiology 

Asthma isn’t just wheeze and puffers — it’s a chronic inflammatory disease of the lower airways, with a complex pathophysiology involving immune dysfunction, airway hyperresponsiveness, structural changes, and reversible obstruction.

🧬 The Key Players

Inflammatory Cells:

• Mast cells release histamine and leukotrienes → bronchoconstriction
• Eosinophils produce cytotoxic proteins → epithelial damage
• Th2 lymphocytes drive the allergic-type inflammation → ↑ IgE, eosinophils
• Neutrophils (especially in severe, non-allergic or adult asthma)
• Dendritic cells present antigens to naïve T cells → polarisation to Th2

Cytokines & Mediators:

• IL-4: Stimulates B cells to class-switch to IgE
• IL-5: Eosinophil growth and activation
• IL-13: Mucus hypersecretion + goblet cell metaplasia
• Leukotrienes, prostaglandins, histamine: Promote bronchospasm, vascular permeability

🚨 Three Cardinal Pathophysiological Features of Asthma:

1. Airway Inflammation

The foundational abnormality. Inflammatory cell infiltration leads to:

• Submucosal oedema
• Epithelial desquamation
• ↑ Mucus production → mucus plugging

This inflammation amplifies airway sensitivity to triggers (allergens, cold air, exercise, viral infection).

2. Airway Hyperresponsiveness (AHR)

This refers to exaggerated bronchoconstriction in response to otherwise innocuous stimuli. Driven by:

• Ongoing inflammation
• Neural dysregulation
• Smooth muscle hypertrophy

AHR explains why even mild exposures can trigger symptoms.

3. Airflow Obstruction

Usually reversible, either spontaneously or with bronchodilators.

Caused by:

• Bronchial smooth muscle constriction
• Mucus hypersecretion
• Mucosal oedema
• Airway wall thickening

Over time, airway remodelling may develop:

• Smooth muscle hypertrophy
• Collagen deposition below the basement membrane
• Goblet cell hyperplasia

These reduce reversibility and increase risk of chronic airflow limitation.

🌿 In Australia, asthma affects ~11% of the population. We’ve got high rates globally – so this is a condition you’ll see a lot.

🧠 MCQ: Test Yourself

Which of the following best explains the role of IL-5 in the pathophysiology of asthma?

• A. It induces B cells to produce IgE
• B. It activates eosinophils and promotes their survival
• C. It triggers bronchial smooth muscle contraction
• D. It increases mucus production from goblet cells
• E. It mediates mast cell degranulation

✅ Correct answer: B. It activates eosinophils and promotes their survival

Explanation:

IL-5 is a signature Th2 cytokine involved in eosinophilic asthma. It plays a central role in promoting the growth, activation, and survival of eosinophils — cells that contribute to epithelial damage, mucus hypersecretion, and chronic inflammation in asthma.

• Option A refers to IL-4, which stimulates B cells to switch to IgE production.
• Option C reflects effects of leukotrienes and parasympathetic stimulation.
• Option D is the role of IL-13, which drives mucus hypersecretion.
• Option E occurs via IgE crosslinking on mast cells, not IL-5.

🩺 Why this matters clinically:

✔️ Explains the rationale behind inhaled corticosteroids as first-line preventers (↓ inflammation)

✔️ Why anti-IL-5 monoclonal antibodies (e.g. mepolizumab) are used in severe eosinophilic asthma

✔️ Justifies spirometry with bronchodilator reversibility testing in diagnosis

✔️ Highlights the importance of early intervention to prevent permanent structural changes

👩‍⚕️👨‍⚕️ You’ll be revisiting asthma again and again — in immunology, physiology, clinical skills, and later in paediatrics, general practice, and ED. Getting a solid grip on the pathophysiology now will pay off big time when you’re diagnosing, explaining treatment plans, and tailoring care for real patients.