1b Asthma and Respiratory Immunology

Question 1

What are the cardinal clinical features of asthma?

Answer 1

Wheeze / dry cough / Dyspnoea

Question 2

What is the definition of asthma?

Answer 2

Reversible airflow obstruction

Question 3

Which part of breathing is affected by asthma?

Answer 3

Expiration - above the X axis on a flow volume loop

Question 4

What happens to the FEV1:FVC ratio is asthma?

Answer 4

reduces

Question 5

What happens to the curve on a flow volume loop in a patient with asthma?

Answer 5

Sinks inwards - moves outwards with the use of a bronchodilator

Question 6

What type of medication pattern is needed to help asthma?

Answer 6

regular doses of anti-inflammatory medication, with increased during an attack - useless as a one off therapy

Question 7

Which immune cell is found in the airways of people with asthma?

Answer 7

Eosinophils

Question 8

What sound will a reversible airflow obstruction make?

Answer 8

wheeze

Question 9

What happens to the the airway wall in a patient with asthma?

Answer 9

Thickening of airway wall due to airway remodelling - eosinophilic inflammation, thicker matrix and thicker smooth muscle

Question 10

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

Answer 10

Some people have sensitization to different allergens, however then a genetic succespibility then determines whether you have asthma or not

Question 11

What is seen when doing GWAS for asthma susceptibility?

Answer 11

Some genes are specifically associated with asthma
However not a single gene which causes – more multifactorial and polygenic

Question 12

Which are the three main interleukins which are prominent in asthma

Answer 12

IL-4, IL-5 and IL-13

Question 13

What do the interleukins produced in allergic asthma cause?

Answer 13

VCAM-1 expression
mast cell proliferation
IgE synthesis
Mucin secretion

Question 14

What is the type of helper cell which is enlisted in allergic asthma?

Answer 14

Type 2 helper cell

Question 15

Which IL increases mucus production?

Answer 15

IL-13

Question 16

What does IL-4 do in allergic asthma?

Answer 16

finds plasma cells to secrete IgE which exacerbates the allergic reaction

Question 17

What are the tests for allergic sensitization?

Answer 17

Blood tests – for specific IgE antibodies to allergens of interest

Total IgE alone not sufficient to define atopy

Question 18

What is an important inflammatory change to look for in Asthma?

Answer 18

Inflammatory eosinophilia

Question 19

What is an abnormal blood eosinophil count for a patient with suspected / confirmed asthma?

Answer 19

> or equal to 300 cells / mcl

Question 20

What is the routine breath test done to test for eosinophilia?

Answer 20

exhale nitric oxide

Question 21

What is an abnormal result for induced sputum eosinophil count?

Answer 21

greater than or equal to 3%

Question 22

What is FeNO?

Answer 22

Fraction of Exhaled Nitric Oxide

Question 23

How is FeNO used diagnostically?

Answer 23

Fractional concentration of exhaled nitric oxide (FeNO) is a quantitative, non-invasive and safe method of measuring airway inflammation and is an indirect marker of T2-high eosinophilic airway inflammation in asthma

Question 24

What is FeNO used to do?

Answer 24

Aid asthma diagnosis
predicting steroid responsiveness
assessing adherance to inhaled corticosteroids

Question 25

What are the three objective tests which should be completed in order to make a clinical diagnosis of asthma?

Answer 25

Airway obstruction on spirometry Reversible airway obstruction Exhaled nitric oxide (FeNO)

Question 26

What is the normal range of REV/FVC ratio in adults and children?

Answer 26

FEV1/FVC ratio <0.7 (adults), <0.8 (children)

Question 27

What percentage change should bronchodilators make to airway obstruction for a diagnosis of asthma to be made?

Answer 27

Bronchodilator reversibility >12%

Question 28

What are the values of exhaled nitric oxide in adults and children which suggest asthma?

Answer 28

>35ppb (children), >40ppb (adults) – in a treatment naïve patient

Question 29

When do you diagnose asthma in children and young people (5-16)?

Answer 29

if they have symptoms suggestive of asthma and: FeNO level of 35 ppb or more and positive peak flow variability or obstructive spirometry and positive bronchodilator reversibility.

Question 30

What is used to reduce airway inflammation?

Answer 30

Inhaled corticosteroids (ICS) Leukotriene receptor antagonists

Question 31

What medications are used for acute symptomatic relief?

Answer 31

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

Question 32

What are the biologics used to target airway eosinophillia?

Answer 32

Anti-interleukin-5 antibody Anti-interleukin-5 receptor antibody

Question 33

Describe the airway of a patient with asthma?

Answer 33

Tightening, inflammation and mucus

Question 34

What medication helps to reduce airway eosinophilia?

Answer 34

steroids

Question 35

How do steroids reduce airway eosinophilia?

Answer 35

1. reducing recruitment from the bone marrow 2. inducing apoptosis in eosinophils

Question 36

What is the benefit of inhaled steroids?

Answer 36

Taken directly to the tissue of interest

Question 37

What is the most important aspect of asthma management?

Answer 37

Optimal edvice and technique Clear asthma management plan Adherence to inhaled corticosteroids

Question 38

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

Answer 38

Allergens + pathogens + pollution + tobacco smoke

Question 39

What happens to PEF in asthma?

Answer 39

Reduced peak expiratory flow rate and increased airway obstruction resulting in an acute wheeze, responsive to bronchodilators

Question 40

What is anti-IgE antibody therapy?

Answer 40

Humanised anti-IgE monoclonal antibody Binds and captures circulating IgE – to prevent interaction with mast cells and basophils to stop allergic cascade

Question 41

What happens to IgE production over time when patients are given anti-IgE Ab?

Answer 41

Decreases

Question 42

Which medication is used for patients with severe, persistent allergic asthma?

Answer 42

Omalizumab

Question 43

Which treatment is an Anti-IL5 antibody?

Answer 43

Mepolizumab

Question 44

What does Mepolizumab do?

Answer 44

Anti-IL5 antibody for severe eosinophilic asthma IL-5 regulates growth, recruitment, activation and eosinophil survival Licenced for adults and children >6 years

Question 45

What are the conditions which patients need to meet in order to be given Mepolizumab?

Answer 45

Blood eosinophils >300 cells/mcl in the last 12 months At least 4 exacerbations requiring oral steroids in the last 12 months Trial for 12 months – 50% reduction in attacks, then continue

Question 46

Which medication only works on people who are extremely eosinophilic?

Answer 46

Mepolizumab

Question 47

What were the effects of treatments with mepolizumab?

Answer 47

Clinically significant exacerbations reduced

Question 48

What happens to the airways and lungs during an asthma attack?

Answer 48

Tightened smooth muscles Air trapped in alveoli wall of airways becomes thickened and inflammed

Question 49

What are the two features of the type of airway inflammation which is seen in asthma?

Answer 49

Eosinophilia Type 2 Lymphocytes