inflammation and immunopathology- asthma

Question 1

What are the 3 airway remodelling changes that occur in the epithelium of an asthmatic?

Answer 1

1. They have missing cells in their epithelium
2. Goblet cell hyperplasia from increased mucous secretion
3. Thickened smooth muscle with lots of collagen in it.

Question 2

Is airway remodelling reversible?

Answer 2

No, it’s largely irreversible

Question 3

Explain fibrosis as a component of airway remodelling.

Answer 3

Fibrosis is when lots of collagen is produced in the smooth muscle layer and the extracellular matrix.

Question 4

What is the effect of fibrosis on the basement membrane?

Answer 4

Fibrosis causes thickening of the basement membrane

Question 5

What is the main consequence of asthmatic changes to the epithelium?

Answer 5

Irritation of the epithelial cells results in:

1. Increased production of fibrogenic growth factors like TGF beta and endothelin.
2. Epithelial-mesenchymal transition

Question 6

Of the three airway remodelling changes, which is the most significant?

Answer 6

Thickening of the smooth muscle layer

Question 7

What is the relationship between angiogenesis and airway remodelling?

Answer 7

There is increased vascularity seen in asthmatics, due to increased angiogenesis.

Question 8

Repeated episodes of asthma cause asthma remodelling. Which ways do they do this?

Answer 8

1. Inflammatory infiltration of mast cells and eosinophils into the lungs.
2. Increased smooth muscle cell proliferation results in tryptase production, which is a profibrotic pathway.
3. Increased goblet and SM cell proliferation.
4. Increased TGF-B secretion leading to increased fibroblast to myofibroblast transformation. This is also a profibrotic pathway.

Question 9

Defective epithelial repair will also induce asthma remodelling. Which ways does it do this?

Answer 9

1. Exposure to allergens like pollen cause epithelial damage through digestive enzymes on their membrane.
2. Digestive enzymes released from eosinophils targeted at the allergen actually damage the epithelium aswell. Eosinophil peroxidase is one example.
3. Neutrophil degranulation and release of enzymes
4. Apoptosis of epithelial cells directed by t-cells.

Question 10

Mechanical stress will also induce asthma remodelling. Which ways does it do this?

Answer 10

1. Increased collagen and fibronectin inside the airways increases the pressure in the airway walls and results in asthma remodelling.

Question 11

Name 3 current asthma treatments.

Answer 11

1. Glucocorticoids
2. Beta receptor agonists, which induce smooth muscle relaxation.
3. Mast cell tryptase inhibitors