Pathophysiology of asthma

Question 1

What is asthma?

Answer 1

Chronic, inflammatory and obstructive disease of the airways, categorised by episodes of reversible airflow limitation and bronchial hyper-responsiveness where the patient finds it difficult to breathe normally (dyspnoea)

Question 2

What are the 2 related components of asthma?

Answer 2

1) Inflammation component
- individual develops hypersensitivity to specific stimulus causing inflammatory response upon subsequent exposures to that stimulus
2) Airway component
- the allergen induced inflammation releases mediators that affect cellular function and airflow, resulting in symptoms like dyspnoea, excess mucus and cough.

Question 3

What is airflow proportional to?

Answer 3

Size of the airway lumen (cross-sectional area and radius)

Question 4

What happens during an asthma attack?

Answer 4

Inflammatory mediators induce pathological changes to the airway causing:

• contraction of airway smooth muscle
• increased mucus secretion
• microvascular leak (causes airway oedema and swelling)

Question 5

What is the pattern of airflow in asthma?

Answer 5

In the presence of airway obstructions during asthma, airflow can become turbulent, increasing resistance and generating wheezing sound.

Question 6

What are the two stages of asthma (how is inflammation produced?)

Answer 6

Stage 1: SENSITISATION
Immune system first encounters the allergen and develops an adaptive immune response

Stage 2: ALLERGIC RESPONSE
Allergen is subsequently re-encountered, triggering the adaptive response previously primed during sensitisation by binding antibodies, which generates an inflammatory response within the airways, producing symptoms

Question 7

Describe the stages of asthma sensitisation. (long answer)

Answer 7

• Allergen is inhaled and enters airway tissue and is engulfed by a macrophage or dendritic cell to become an APC
• APC encounters a naive T helper cell and the antigen is presented to the T helper cell, enabling it to mature into a Th2 cell
• Activated Th2 cell then interacts with a B cell to initiate class switching, proliferation and production of IgE antibodies that bind the antigen present in the original allergen
• IgE antibodies circulate and bind to IgE receptors on mast cells, which contain pro-inflammatory mediators such as histamine, leukotrienes and prostaglandins
• Th2 cells will also secrete IL4, IL5 and IL13 which act to modulate the immune system. IL5 in particular promotes survival, proliferation and trafficking of eosinophils.

Question 8

Explain the stages of the asthmatic allergic response (long answer).

Answer 8

• Upon subsequent re-exposures to the allergen, the antigens within the allergen are recognised by the IgE molecules bound to the mast cells within the airways, triggering degranulation, where mast cells releases its inflammatory mediators (prostaglandins, cytokines, leukotrienes)
• Mediators can bind to receptors on multiple cell types within the airways, causing contraction of airway smooth muscle, microvascular leak (oedema) and activation of goblet cells (mucus secretion)
• Causes bronchospasm and decreased airflow
• Several hours later as well Th2 cells release IL4, IL5 and IL13 and eosinophils release reactive oxygen species, leukotrienes and toxic enzymes, further decreasing airway function until inflammation is resolved

Question 9

What is the early asthmatic response to an allergen?

Answer 9

Acute bronchoconstriction brought about by the initial wave of degranulation. It occurs around 0-1 hours in.

Question 10

What is the late asthmatic response?

Answer 10

Symptoms initially improve before worsening, brought about by a secondary inflammation and migration of Th2 and eosinophils to the airways.
Individual is more sensitive to attacks in this period.
Occurs up to 12 hours in

Question 11

What is chronic asthma?

Answer 11

When the response occurs with repeated waves of inflammation and tissue damage, resulting in airway tissue remodelling (irreversible).

Question 12

What effect does chronic asthma have?

Answer 12

• Airways are permanently constricted
• Causes smooth muscle hypertrophy
• Increased number of goblet cells and activated mucus glands secreting more mucus
• Further infiltration and proliferation of immune cells within airways, causing more epithelium disruption and easier access for allergens
• Basement membrane thickness and possible fibrosis