ASTHMA AND RESPIRATORY IMMUNOLOGY

Question 1

What are the cardinal features of asthma?

Answer 1

Wheeze with/out dry cough
Atopy/allergen sensitisation
Reversible airflow obstruction
Airway inflammation: eosinophilia/type 2 - lymphocytes

Question 2

What 3 cardinal features do you test for the diagnosis of asthma?

Answer 2

Atopy/allergen sensitisation
Reversible airflow obstruction
Airway inflammation: eosinophilia/type 2 - lymphocytes

Question 3

Why do individuals with asthma experience wheezing?

Answer 3

Due to turbulent flow of air through decreased lumen of airways

Question 4

What would the flow volume loop of a patient with asthma look like?

Answer 4

Check notes: obstructive flow volume loop

Question 5

Explain the pathogenesis of allergic asthma

Answer 5

Pollen/dustmites/mold stimulate the bronchial epithelium causing inflammation and airway remodelling (changes to structural cells)
——>
Increased goblet cells
More matrix laid down
Increased amount and size of smooth muscle cells
Eosinophilia

Question 6

Why do only some people who have been sensitized develop asthma?

Answer 6

These people have genetic susceptibility

Question 7

Describe the genetics of susceptibility of asthma

Answer 7

Multi gene disorder and polyfactorial

Most common genes: GSDMB, IL33

Question 8

Describe how type 2 immunity sensitisation occurs in allergic asthma and explain the reaction

Answer 8

Antigen presented on APCs (dendritic cells in lung) by MHC class II.
Presented to Th0 cells which differentiates to Th1 and Th2.
Th2 secrets Il-4, Il-13, Il-5 causing:
Mast cell proliferation, IgE synthesis, Mucin secretion, Eosinophilic airway inflammation, VCAM-1 expression

Question 9

What is IL-5’s function in allergic asthma?

Answer 9

Recruits eosinophils and promotes eosinophils survival

Question 10

What is IL-4’s function in allergic asthma?

Answer 10

Helps conversion of plasma cells to secrete IgE

Question 11

What is IL-13’s function in allergic asthma?

Answer 11

Involved in mucus production

Question 12

How does the inflammation in an allergic inflammation work?

Answer 12

When cells exposed to allergen again:

• IgE produced and binds to mast cells and the allergen causing degranulation
• Growth factors, cytokines, chemokines released

Question 13

What test is used for allergic sensitization?

Answer 13

Skin prick tests
+ve control - histamine
-ve control - saline

Question 14

What are the tests for eosinophilia and their results?

Answer 14

Abnormal blood eosinophil count when stable
>= 300 cells/mcl

Abnormal induced sputum eosinophil count
>= 2.5%

Exhaled nitric oxide

Question 15

What is a non-invasive test for type 2 eosinophilic airway inflammation?

Answer 15

Fraction of exhaled nitric oxide (FeNO)

Question 16

What result of FeNO can diagnose asthma?

Answer 16

Elevated FeNO provided patient isn’t on steroids as they suppress nitric oxide down to normal levels

Can also be used to assess if patient is taking medication and adherence to inhaled corticosteroids

Question 17

What are the NICE tests that can be done to diagnose asthma and their corresponding results?

Answer 17

Clinical assessment:

• history and examination
• assess/confirm wheeze when acutely unwell

Objective tests:
- FEV1/FVC ratio < 0.7 (obstruction)
- Bronchodilator reversibility >= 12% (reversible airway
obstruction)
- FeNO > 35 ppb (children) or > 40 ppb (adults)

Question 18

What is the recommended NICE order of diagnostic tests for asthma?

Answer 18

Spirometry and then bronchodilator reversibility (BDR) test if spirometry shows obstruction

If still uncertain after spirometry and BDR - FeNO
If still uncertain after FeNO, monitor peak flow variability for 2-4 weeks

Question 19

What are the diagnosis criteria for asthma in children and young people

Answer 19

Symptoms suggestive of asthma +
- FeNO level of 35 ppb+ and +ve peak flow variability
or
- Obstructive spirometry and +ve bronchodilator reversibility

Question 20

What are the 3 levels of asthma management?

Answer 20

1. Anti eosinophilic inflammatories (baseline therapy that all patients should be on)
2. Acute symptomatic relief
3. Severe asthma - steroid sparing therapies

Question 21

Give 2 examples of anti eosinophilic inflammatories

Answer 21

• Inhaled corticosteroids (ICS)

- Leukotriene receptor antagonists

Question 22

Give 2 examples of drugs which provide acute symptomatic relief of asthma

Answer 22

• Beta-2 agonists (smooth muscle relaxation)
• Anticholinergic therapies (smooth muscle relaxation)

Don’t use regularly
If used without anti-inflammatory can lead to asthma death

Question 23

Give 2 examples of drugs which used to treat severe asthma and are steroid sparing

Answer 23

• Biologic targeted to IgE (anti-IgE antibody)
• Biologics targeted to airway eosinophils
  (Anti-IL-5 antibody, anti-IL-5 receptor antibody)

Question 24

How do corticosteroids help in asthma?

Answer 24

Reduce type II inflammation

Helps in remodelling

Question 25

How does anti-IgE antibody therapy work?

Answer 25

anti-IgE antibody binds to IgE preventing it from interaction with mast cells and basophils preventing degranulation

IgE production can decrease with time if given meaning the therapy may not need to be used indefinitely
However no evidence that it can cure

Question 26

Name one anti-IgE antibody

Answer 26

Omalizumab

Question 27

Who is omalizumab given to and what is it’s dosing based on?

Answer 27

Patients with severe, persistant allergic asthma
>= 6 years who need frequent corticosteroid treatment (4 or more courses in the previous year)

Patients who have been given optimised standard therapy and still don’t respond

Total serum IgE: 30-1500

Dosing based on weight and serum IgE 2-4 weekly s/c injections

Question 28

Name an anti-IL5-antibody

Answer 28

Mepolizumab

Question 29

Who is given mepolizumab?

Answer 29

Patients with severe eosinophilic asthma
Blood eosinophils >= 300 cells/mcl in last 12 months
At least 4 exacerbations requiring oral steroids in last 12 months

Trial for 12 months - if 50% reduction in attacks then continue