CVR - Asthma and respiratory immunology

Question 1

What are the cardinal features of asthma?

Answer 1

• Wheeze/dry cough
• Atopy/allergen sensitisation
• Reversible airflow obstruction
• Airway inflammation

Question 2

Describe the pathogenesis of asthma

Answer 2

• Normal airway smooth muscle is exposed to an allergen
• This results in the recruitment of inflammatory cells - mainly eosinophils
• As well as this the epithelium undergoes a structural change and the amount of matrix increases
• This inflammation and increases size of matrix and endothelium results in an inflamed airway

Question 3

What must be present for a patient to develop asthma?

Answer 3

An underlying genetic succeptibility

Question 4

Describe the mechanism of type 2 immunity in allergic asthma

Answer 4

• Antigen presented to dendritic cell
• The APC then, on MHC class II, takes the antigen to the thymus where the naive T cells are
• These T cells then differentiate in Th2 cells
• The Th2 cells contain IL-4, IL-5, IL-13 which cause the manifestations of asthma

Question 5

What molecule causes the recruitment of the eosinophils to the airways?

Answer 5

IL-5

Question 6

What effect does IL-4 cause?

Answer 6

• IL-4 causes B cells to release IgE
• When a person is exposed to the allergen again, the IgE activates mast cells
• The activation of these results in degranulation of the mast cell and then allergic asthma

Question 7

How are allergies tested for?

Answer 7

Skin test:

• Intradermal injections
• Saline and histamine used as negative and positive test
• The allergens are then injected and compared to the controls

Blood test:

• Test for specific IgE antibodies to allergens of interest
• However TOTAL IgE not sufficient to define atopy

Question 8

How do you test for asthma?

Answer 8

• Blood eosinophil count - If raised at normal health, indicative of asthma
• Induced sputum eosinophil count
• Exhaled nitric oxide - high is indicative, PROVIDED NOT ON STEROIDS

Question 9

What are the tests done clinically for asthma?

Answer 9

• Airway obstruction on spirometry
• Reversible airway obstruction
• Exhaled nitric oxide

Question 10

What treatments can be given to patients with asthma?

Answer 10

1. Reduce airway eosinophilic inflammation:
   
   • Inhaled corticosteroid
   • Leukotriene receptor agonists
2. Acute Symptomatic relief:
   
   • Beta-2 agonists (smooth muscle relaxation)
   • Anticholinergic therapies (smooth muscle relaxation)
3. Severe asthma - steroid sparing therapies:
   
   • Biologic targeted to IgE
     
     • Anti-IgE antibody
   • Biologics targeted to airway eosinophils
     
     • Anti-interleukin-5 antibody
     • Anti-interleukin-5 receptor antibody

Question 11

What do inhaled corticosteroids do?

Answer 11

• Reduce eosinophil level via inducing apoptosis
• Recuce type 2 mediators released by the Th2 cells
• Reduce mast cell numbers

Question 12

Describe asthma management

Answer 12

• Provide patient with the optimal device
• Teach them the proper technique of using an inhaler
• Give the patient a clear asthma management plan for when they are healthy or feeling unwell
• Make sure the patient knows they must adhere to the inhaled corticosteroids, even when they are feeling well

Question 13

What can cause an asthma attack?

Answer 13

Exposure to:
- Allergens
- Pathogens
- Pollution 
and potentially a sudden exposure to a chemical, e.g. tobacco smoke

All have to happen

Question 14

What is anti-IgE antibody therapy?

Answer 14

• Humanised anti-IgE monoclonal antibodies bind and capture circulation IgE - prevents interaction with mast cells and basophils to stop allergic cascade
• IgE production can be reduced after prolonged doses
• However if treatment is stopped, symptoms and asthma come back with time

Question 15

What is mepolizumab?

Answer 15

It is a anti-IL-5 antibody