Asthma and respiratory immunology

Question 1

What are the cardinal features of asthma? (3)

Answer 1

-Atopy / allergen sensitisation
-Reversible airflow obstruction
-Airway inflammation
Eosinophilia
Type 2 - lymphocytes

Question 2

What type of immune cells do you see infiltrating asthmatic airways?

Answer 2

Eosinophils

Question 3

Describe the pathogenesis of allergic asthma

Answer 3

-An allergen gets introduced into the airway bronchial epithelium which sensitizes it causing, inflammation and remodeling.
-Recruitment of inflammatory cells (mostly eosinophils) leads to increase in mucous secreting goblet cells.
-Amount of MATRIX and MUSCLE CELL SIZE then increase.

Question 4

Why are only some people who are sensitised develop the disease of asthma?

Answer 4

Due to genetic susceptibility to asthma

Question 5

Circled genes are more expressed in asthma patients

• What does this show about the genetic cause of asthma?

Answer 5

That it’s a multigene disorder and is polyfactorial

Question 6

What does MHC stand for and what is MHC class II and its function

Answer 6

Major histocompatibility complex:
-It is present on the surface of certain immune cells, such as dendritic cells, B cells, and macrophages

-Presents antigens to T helper cells

Question 7

How does type 2 immunity reaction come about in allergic asthma? (3 STEPS)

Answer 7

• Patients with asthma have exposure to inhaled allergen
• This allergen binds to lung dendritic cells and are carried via MHC class II to mediastinal lymph nodes
• Naive T cells in nodes differentiate into Th2 cell which secretes IL4, 5 and 13

Question 8

What does IL-4 do?

Answer 8

Helps conversion of B plasma cells to secrete IgE

Question 9

What does IL-5 do?

Answer 9

IL-5 recruits eosinophils into airways and promotes their survival- causing eosinophilia

Question 10

What does IL-13 do?

Answer 10

Involved in mucous production

Question 11

If a patient is already sensitised to allergen- what happens if they’re exposed to it again?

Answer 11

• There’s an allergic immune response
• IgE recognises circulating antigen and binds to mast cells
• Mast cells degranulate and release histamines, cytokines, chemokines, growth factors, enzymes, eicosanoids

Question 12

How do we test for allergic sensitisation? (2) (what reaction to we look for)

Answer 12

-Blood tests for specific IgE antibodies
-Allergy skin prick tests, look for WHEAL AND FLARE REACTION.

Question 13

How do we test for eosinophilia? (3)

Answer 13

• Blood eosinophil count when stable → ≥300 cells/mcl is abnormal
• Induced sputum eosinophil count: ≥2.5% eosinophils is abnormal
• Exhaled nitric oxide

Question 14

What objective tests are done to diagnose asthma? (3)

Answer 14

• Airway obstruction on spirometry- FEV1/FVC ratio <0.7
• Reversible airway obstruction- bronchodilator reversibility ≥12%
• Exhaled NO (FeNO) >35ppb (children), >40ppb (adults)

Question 15

What are the 3 areas of asthma management?

Answer 15

-Reduce airway eosinophilic inflammation
-Acute symptomatic relief
-Treat severe asthma

Question 16

How do we reduce airway eosinophilic inflammation?

Answer 16

• Inhaled corticosteroids- target and reduce eosinophilic inflammation
• Leukotriene receptor antagonists- can reduce type 2 inflammation

Question 17

How do we give acute symptomatic relief?

Answer 17

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

Question 18

How do we treat severe asthma?

Answer 18

Steroid sparing therapies

• Biologics targeted to IgE e.g. anti-IgE antibody
• Biologics targeted to airway eosinophils e.g. anti-interleukin-5 antibody and anti-interleukin-5 receptor antibody

Question 19

Why do we use corticosteroids? (what things do they do?) (2)

Answer 19

• Reduce eosinophil numbers through apoptosis
• Reduce mast cell numbers

Question 20

How do we measure adherence objectively?

Answer 20

Electronic adherence monitoring

Question 21

What is the order of treatment for asthma patients?

Answer 21

Question 22

How do we treat acute asthma attacks?

Answer 22

• With systemic high dose steroids like prednisolone
• Inhaled steroids in maintenance therapy isn’t good enough

Question 23

How does anti-IgE antibody therapy work?

Answer 23

• Binds and captures circulating IgE- prevents its interaction with mast cells and basophils to stop allergic cascade
• IgE production can decrease with time when patients given anti-IgE Ab

Question 24

What is Omalizumab?

Answer 24

• The commonly used anti-IgE antibody given as subcutaneous injections
• Is very expensive
• Is effective at reducing exacerbations compared to placebo

Question 25

When is omalizumab used?

Answer 25

Severe, persistent allergies (IgE mediated) asthma in patients ≥6 years who need continuous or frequent treatment with oral corticosteroids

Have to have optimised standard therapy with good adherence with no response

Question 26

What serum IgE level is Omalizumab prescribed for?

Answer 26

Total serum IgE between 30-1500

Question 27

What is Mepolizumab?

Answer 27

• Anti-IL5-antibody
• Reduces IL-5 effect, reducing eosinophilic inflammation in severe eosinophilic asthma

Question 28

When is Mepolizumab trialed?

Answer 28

Blood eosinophils ≥300 cells/mcl in the last 12 months

At least 4 exacerbations requiring oral steroids in the last 12 months