Cardio - Asthma and Respiratory Immunology

Question 1

Describe the epidemiology of asthma

Answer 1

Affects 5.4 million people in the UK
1 million children affected
3 people die every day in UK
£1 billion spent by NHS annually

Question 2

What are the 4 cardinal features of asthma

Answer 2

1. Wheeze ± dry cough (+ shortness of breath or dyspnoea)
2. Allergen sensitisation/atopy
3. Reversible airway obstruction
4. Airway inflammation

Question 3

What may be associated with the dry cough along with the wheeze

Answer 3

Worse on exertion, with colds or with allergen exposure

Question 4

What is associated with airway inflammation

Answer 4

Eosinophilia

Type 2 lymphocytes

Question 5

What are the 3 objective things we use for the diagnosis of asthma

Answer 5

Allergen sensitisation/ atopy
Reversible airway obstruction
Airway inflammation

Question 6

What does a patent airway allow for?

Answer 6

Laminar flow of air

Question 7

What type of airway does an asthmatic have even if they are well without treatment

Answer 7

Thickened airway due to wall inflammation and tightened smooth muscles

Question 8

What causes the wheeze in asthma

Answer 8

Turbulent flow

Question 9

How do we check for reversible airway obstruction

Answer 9

Spirometry with the use of bronchodilators

Question 10

Describe the flow vol loop of an asthmatic

Answer 10

We see coving when they patient is breathing out indicating airway obstruction. This is because of an increased resistance in the airway reducing flow rate

Question 11

What should we see happen in the loop if an asthmatic is given bronchodilators

Answer 11

We should see the coving turn into a more straight laminar flow on the FVL

Question 12

What does the patient need to do when doing spirometry

Answer 12

Wear nose clips and do a forced expiratory manoeuvre

Question 13

What do children need in spirometry

Answer 13

Incentive device for cooperation

Question 14

What do we look for in terms of airway inflammation?

Answer 14

Eosinophilia

Question 15

What is a local allergen challenge?

Answer 15

When we inject an allergen directly into the airway of a sensitised asthma patient, we see inflammation, swelling and narrowing of the airway after around 10 minutes

Question 16

What are the 2 stages of allergic asthma pathogenesis

Answer 16

1. Sensitisation and exposure to allergens

2. Parallel inflammation and remodelling of the airway

Question 17

With airway remodelling what do we see

Answer 17

• Increased size and number of smooth muscle cells in airway.
• Increase in matrix size
• Increase in goblet cells in the epithelium to increase mucus production

Question 18

In airway inflammation what do we see

Answer 18

Recruitment of inflammatory cells, mainly eosinophils

Question 19

Why do only some people who are sensitised develop asthma?

Answer 19

There is genetic susceptibility combined with environmental exposures (allergen, infection, pollution)

Question 20

What genes may be associated with susceptibility to asthma

Answer 20

IL33 and GSDMB - patients have multiple mutations

Question 21

What type of immunity is associated with allergic asthma?

Answer 21

Type 2

Question 22

How does sensitisation happen in allergic asthma?

Answer 22

Inhaled allergen acts as an antigen which is presented to the DCs of the lungs (APC). DCs then carry them to mediastinal lymph nodes where naive Th0 cells differentiate to Th2 to secrete IL4 IL5 IL13.

Question 23

What does IL5 do

Answer 23

Recruits eosinophils and promotes their survival

Question 24

What does IL4 do

Answer 24

Helps the conversion of plasma cells to secrete IgE

Question 25

What does IL13 do

Answer 25

Promotes mucin secretion

Question 26

After sensitisation, what happens if antigen exposure happens again?

Answer 26

Antigen is recognised by specific IgE. These then bind to mast cells to degranulate them and give an allergic reaction

Question 27

What do mast cells release when degranulated

Answer 27

Histamines, eicosanoids, cytokines, chemokines, enzymes, growth factors

Question 28

What are the 2 main tests for allergic asthma?

Answer 28

Skin prick test | IgE test

Question 29

What is the skin prick test?

Answer 29

Intradermal injection of positive control (histamine) and negative control (saline), and then house dust mites, dander etc. We then measure response with wheel and flare

Question 30

What is the IgE test?

Answer 30

We test the blood for specific IgE antibodies

Question 31

What tests can we use for eosinophilia?

Answer 31

Stable blood eosinophil count Induced sputum eosinophil count Exhaled nitric oxide

Question 32

What is an abnormal blood eosinophil count when normal

Answer 32

≥300 cells/mcl

Question 33

What is an abnormal induced sputum eosinophil count

Answer 33

≥2.5% eosinophil

Question 34

What is a contraindication to using exhaled nitric oxide test

Answer 34

If they are using steroids

Question 35

What else can FeNO be used for?

Answer 35

Measuring compliance of ICS

Question 36

What are the NICE steps for asthma diagnosis?

Answer 36

Clinical assessment | Objective tests

Question 37

What do we do in our clinical assessment?

Answer 37

History Examination Assess/confirm wheeze when they are acutely unwell

Question 38

What are our objective tests?

Answer 38

Obstruction - FEv1/FVC Reversible obstruction- bronchodilator reversibility (BDR) FeNO

Question 39

What is the diagnosis for FEV1/FVC

Answer 39

<0.7

Question 40

What is the diagnosis for Bronchodilator reversibility on obstruction?

Answer 40

≥12%

Question 41

What is the diagnosis for FeNO in adults

Answer 41

>40 ppb

Question 42

What is the diagnosis for FeNO in children

Answer 42

>35 ppb

Question 43

How many tests do we need to confirm our diagnosis

Answer 43

2

Question 44

When do we need to test spirometry or peak expiratory flow?

Answer 44

We need to test these over 2 weeks to show variability

Question 45

What are the preferred tests for asthma

Answer 45

Spirometry | Consider BDR if spirometry shows obstruction

Question 46

If we can't do BDR or spirometry, what should we do.

Answer 46

If child - treat based on prior findings and try again in 6-12 months If not - consider FeNO

Question 47

If FeNO doesn't help with diagnosis, what do we do

Answer 47

Monitor peak flow variability for 2-4 weeks

Question 48

What is the aim of basic maintenance therapy?

Answer 48

Reduce airway inflammation

Question 49

What do we include in basic maintenance therapy?

Answer 49

1. Inhaled corticosteroids (ICS - reduce eosinophils) | 2. Leukotriene receptor antagonist - reduces type 2 inflammation

Question 50

What is the aim of acute symptomatic relief?

Answer 50

Smooth muscle relaxation

Question 51

What do we include in acute symptomatic relief?

Answer 51

1. Beta-2 agonist | 2. Anticholinergic therapies

Question 52

What steroid sparing therapies can we use for severe asthma?

Answer 52

Biologics to target IgE or for airway eosinophils

Question 53

What biologics do we have for targeting airway eosinophils

Answer 53

Anti IL5 antibody | Anti IL5 receptor antibody

Question 54

What is the prime function of inhaled corticosteroids?

Answer 54

Induce apoptosis of eosinophils to reduce inflammation

Question 55

How do ICS affect Th2?

Answer 55

Reduce the release of cytokines and mediators

Question 56

How do ICS affect mast cells?

Answer 56

Reduce numbers

Question 57

How do ICS affect epithelial cells

Answer 57

Reduce cytokines and mediators

Question 58

How do ICS affect endothelial cells

Answer 58

Reduce leaking

Question 59

How do ICS affect airway SMC?

Answer 59

Reduce cytokines and increase beta receptors

Question 60

How do ICS affect mucus glands

Answer 60

Decrease mucus secretion

Question 61

How can we assess adherence accurately?

Answer 61

Ensure optimal device and technique, and we can attach an electronic device to their ICC inhaler to measure how often they're taking the dose

Question 62

What is the threshold for giving ICS ± leukotriene receptor antagonist

Answer 62

Even if an adult of child has mild asthma, they are still given maintenance therapy

Question 63

What is a common scenario whereby someone with asthma dies?

Answer 63

Someone people fine therefore don't take their maintenance therapy and suddenly they become exposed to an allergens causing an acute lung attack and thus death in some cases

Question 64

What is the altered immune response underlying an acute lung attack?

Answer 64

1. Increased inflammation, especially alarming (e.g. IL33) 2. Decreased IFN-1/3 release and response 3. Increased mast cell degranulation 4. Increased eosinophil recruitment 5. Increased mucus production 6. Decreased CD8 and Th1 responses 7. Increased Th2 response 8. Increased viral replication and slower clearance

Question 65

What is the effect of an acute lung attack in school age children

Answer 65

Severity of illness is worse: - Acute wheeze - Eosinophilia is worse

Question 66

How do we treat an acute lung attack

Answer 66

High dose of systemic steroids

Question 67

When do we start anti-IgE therapy

Answer 67

When there is severe asthma that doesn't respond to ICS or maintenance therapy

Question 68

What is anti-IgE therapy?

Answer 68

Humanised monoclonal anti-IgE antibody that binds to circulating IgE to prevent interaction with mast cells thus preventing the allergic cascade

Question 69

Why may anti-IgE therapy not be used indefinitely?

Answer 69

IgE production may decrease over time with biologic therapy therefore there is less need for it

Question 70

What is the criteria for starting someone on Omalizumab?

Answer 70

- Severe persistent IgE mediated asthma - 6+ years old - Optimised standard therapy w/ no response despite good adherence - Frequent exacerbations

Question 71

What are the limitations of omalizumab?

Answer 71

- Need a specific IgE range to start - most people don't have this (30-1500) - Very expensive treatment

Question 72

What is the dosage of omalizumab?

Answer 72

Based on weight and serum IgE but normally 2-4 weekly subcutaneous injections

Question 73

What is Mepolizumab?

Answer 73

Anti-IL5 antibody that regulates the growth, survival, activation and recruitment of eosinophils.

Question 74

What is mepolizumab used for?

Answer 74

It is used for severe eosinophilic asthma

Question 75

What is the criteria for mepolizumab?

Answer 75

- ≥300 eosinophils/mcl in the last year - 4 exacerbations in the last 12 months requiring oral steroids - After an oral trial for 12 months - you need at least 50% reduction in attacks for continuation

Question 76

How do we know Anti-IL5 antibodies are effective in asthma?

Answer 76

DREAm trial showed efficacy of anti IL5 antibodies for severe asthma