Asthma and Respiratory Immunology

Question 1

What are the cardinal features of asthma?

Answer 1

Wheeze +/- Dry cough - on exertion, worse w/ colds/ allergen exposure
Atopy / allergen sensitisation
Reversible airflow obstruction
Airway inflammation (Eosinophilia, type 2 - lymphocytes)

Question 2

Draw a flow volume loop for reversible airflow obstruction.

Answer 2

PPT1 SLIDE 6

Question 3

Compare asthmatic airway and asthmatic airway during attack.

Answer 3

asthmatic: relaxed smooth muscle, wall inflamed/thickened, mucus, asthmatic under attack: air trapped in alveoli, tightened smooth muscles, wall inflamed/thickened, mucus

Question 4

Pathogenesis of allergic asthma

Answer 4

allergen > inflammation/airway remodelling > thick matrix, increased immune cell recruitment

Question 5

Why do only some people who are sensitized develop disease (asthma)?

Answer 5

genetic susceptibility

environmental exposures

Question 6

Briefly outline type 2 immunity in allergic asthma.

Answer 6

antigen > MHC II (APC) > Th0 > Th2>

1. > IL-5 > eosinophilic airway inflammation
2. > IL-4, IL-13 > VCAM-1 expression, mast cell proliferation, IgE synthesis, mucin secretion

Question 7

Tests for allergic sensitization

Answer 7

Blood tests – for specific IgE antibodies to allergens of interest

Total IgE alone not sufficient to define atopy

Question 8

Tests for eosinophilia

Answer 8

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

Question 9

What is a method of measuring airway inflammation?

Answer 9

fractional concentration of exhaled nitric oxide

Question 10

Benefits to FeNO

Answer 10

quantitative
safe
non invasive

Question 11

Role of FeNO

Answer 11

aiding asthma diagnosis
predicting steroid responsiveness
assessing adherence to inhaled corticosteroids

Question 12

FeNO is an indirect marker of what?

Answer 12

T2 high eosinophilic airway inflammation in asthma

Question 13

NICE asthma clinical assessment guidelines

Answer 13

history + examination

assess/confirm wheeze when acutely unwell

Question 14

NICE asthma objective tests diagnosis guidelines

Answer 14

Airway obstruction on spirometry - FEV1/FVC ration <0.7
Reversible airway obstruction - Bronchodilator reversibility >12%
Exhaled nitric oxide

Question 15

Diagnose asthma in children and young people (aged 5to16) if they have symptoms suggestive of asthma and?

Answer 15

FeNO level >35ppb + +ve peak flow variabilityor obstructive spirometry + +ve bronchodilator reversibility

Question 16

Management of asthma includes?

Answer 16

reduce airway eosinophilic inflammation, acute symptomatic relief, severe asthma - steroid sparing therapies

Question 17

How to reduce airway eosinophilic inflammation?

Answer 17

inhaled corticosteroids

leukotriene receptor antagonists

Question 18

How to achieve acute symptomatic relief for asthma?

Answer 18

beta-2 agonists anticholinergic therapies

both for smooth muscle relaxation

Question 19

What are steroid sparing therapies for management of severe asthma?

Answer 19

biologic targeted to IgE (anti IgE antibody)
biologics targeted to airway eosinophils
Anti-IL-5 antibody
Anti-IL-5 receptor antibody

Question 20

Corticosteroids work on what inflammatory cells?

Answer 20

eosinophils
t-lymphocytes
mast cells
macrophages
dendritic cell

Question 21

Corticosteroids work on what structural cells?

Answer 21

epithelial
endothelial
airway smooth muscle
mucus gland

Question 22

What effect do corticosteroids have on inflammatory cells?

Answer 22

reduce their numbers

reduce their cytokines

Question 23

What effect do corticosteroids have on structural cells?

Answer 23

decrease mucus, mediator, cytokine production
decrease leakage from endothelial cells
upregulates B2 receptors on smooth muscle

Question 24

What are the most important aspect of asthma management?

Answer 24

optimal device and technique
clear management plan
adherence to inhaled corticosteroids

Question 25

Average adherence to ICS?

Answer 25

33%

Question 26

Pathogenesis of acute asthma attack?

Answer 26

allergens/pathogens/pollution/tobacco smoke > increased airway eosinophilic inflammation, reduced IFN anti viral response

Question 27

What is anti-IgE antibody therapy for?

Answer 27

Binds and captures circulating IgE – to prevent interaction with mast cells and basophils to stop allergic cascade

Question 28

How can IgE production change with anti-IgE antibody therapy over time?

Answer 28

IgE production can decrease > therapy may not need to be used indefinitely

Question 29

What is Omalizumab?

Answer 29

anti-IgE antibody

Question 30

What is Mepolizumab?

Answer 30

anti-IL5-antibody

Question 31

Current UK recommendations for omalizumab?

Answer 31

Severe, persistent allergic asthma in patients >6 yrs who need cont/ freq tx w/ OCS (4 or more courses in the previous year)

Optimised standard therapy

Documented compliance

Question 32

Omalizumab dosing is based on?

Answer 32

weight

serum IgE

Question 33

IL-5 regulates what?

Answer 33

growth, recruitment, activation, eosinophil survival

Question 34

Current UK recommendations for mepolizumab

Answer 34

Severe eosinophilic asthma

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

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