Asthma

Question 1

How are the changes to airway function are relatively consistent between asthma patients, whereas the characteristics of the inflammation can vary considerably?

Answer 1

There is variation in the degree of cough, the age of the onset of the asthma and the degree of remodelling, But these are relatively consistent

What differs is the inflammatory response:
-Different levels of eosinophils, T cells and IGE

higher levels of these cells were not associated with more severe asthma

Question 2

Asthma syndrome vs phenotypes vs endotypes

Answer 2

Asthma syndrome: characterised by variable and recurring symptoms: air flow obstruction, bronchial hyper responsiveness, and inflammation

Asthma phenotypes: characterised by variable observable characteristics: early or late onset, specific triggers

Asthma endotypes: characterised by distinct pathophysiological mechanisms -eg. T2 high or T2 low

Question 3

6 types of asthma (type 2 high)

Answer 3

1. Early onset asthma
   cause: allergin sensitation
   Inc IgE, Inc. Th2, Inc eiosinophils
2. Late-onset eiosophillic asthma
   cause: stappylococcus enterotoxin
   Inc eisinophils Inc. specific IgE
   - steroid refractory
3. Asprin exaccerbated respiratory disease
   cause: dysregulated aracionic acid metabolsm
   Inc eiosophils

Question 4

6 types of asthma (type 2 low)

Answer 4

Obesity associated asthma
risk factors: female, middle age
- inc IL6, Inc neutrophils

smoking associated asthma
cause: Inc. ROS
Inc neutrophils

very late onset asthma
onset after 50 or 60
cause: ageing causing a decline in immune system function
Inc. neutrophils

Question 5

Why does it matter if there are underlying differences in inflammation?

Answer 5

• Allow us to develop targeted therapies for specific endotypes- develop personalised medicine
• Impact on research both for the pathophysiology and also the development of novel treatments (e.g. need to choose whether one is researching broad spectrum treatments/general pathology or endotype specific)

Question 6

The role of epithelial cells and innate lymphoid cells

Answer 6

The allergens can directly cause damage to the epithelial cell layer.

The epethelial cell layer has PRR that recognise conserved regions on the allergen

The epethelial cells release Alarmins

Alarmins (cytokines) activate GROUP 2 inate lymphoid cells

which prod IL5

Question 7

Pathophysiology of Asthma

Answer 7

The allergen is phagocytosed by dendritic cells. The dendritic cell presents the allergen on a MHC-2 molecule. The MHC-2 molecule interacts with cd4 molecule on the T cell and the T cell receptor interacts with the allergen. This causes the release of the cytokines IL4 and IL5.

IL4– binds to FER-1 receptor on plasma cells – produces IgE antibody— IgE binds to mast cells—- degranulation— Leukotrines and HISTAMINE

IL-5— eiosinophils—- release Leuotrines and Proteases.

Histamines and leukotrines function:
- causes smooth muscle constriction in the bronchioles
- Dilation of the cappillaries - blood vessels become increasingly permeable -
excess mucus secretion and inflammation