asthma and respiratory immunology

Question 1

epidemiology of asthma in uk

Answer 1

5.4 mill people currently receiving treatment
1.1 mill children affected
3 people die of asthma a day
nhs spends 1 bill annually

Question 2

what are the cardinal features of asthma

Answer 2

1.wheeze with or without dry cough
- made worse on exercise, allergen exposure or respiratory infections
breathlessness
2. atopy/allergen sensitisation
3. reversible airflow obstruction
4. airway inflammation - eosinophils,lymphocytes

Question 3

what is the pathophysiology of asthma

Answer 3

thickened airway wall caused by inflammation
increase in airway smooth muscle
airway lumen narrowed

Question 4

what causes wheezing

Answer 4

airways narrowed - causes turbulent flow

Question 5

how can we look for reversible airway obstruction

Answer 5

most common lung function test is spirometry

Question 6

what mostly causes airway inflammation

Answer 6

eosinophils

Question 7

why are nose clips worn during spirometry

Answer 7

so exhalation is just through mouth

Question 8

what is the pathogenesis of allergic asthma

Answer 8

first exposed to allergen and sensitised
causes airway remodelling:
recruitment of inflammatory cells e.g eosinophils
increased goblet cells - mucus
more matrix secreted
amount and size of muscle cells increased

Question 9

why are only some who are sensitised develop asthma

Answer 9

genetic susceptibility

with environmental exposure leads to airflow obstruction

Question 10

how do we know that asthma involved genetic susceptibilty

Answer 10

genome wide association studies
e.g il1r1
rad50
il33 !
gsdmb !

asthma is a multi gene disorder

Question 11

describe type 2 immunity in allergic asthma

Answer 11

antigen binds to mhc2 on apc
th0 differentiate to th2 and th1
th2 secretes 1l4,5,13
results in allergic reaction - histamines,mediators…

Question 12

what is role of il5

Answer 12

recruits eosinophils in airways and promotes eosinophil survival

Question 13

what is role of il4

Answer 13

helps conversion of b cells/ plasma cells to secrete ige

Question 14

what is il 13 involved in

Answer 14

mucus secretion

Question 15

how to look for evidence of allergen sensitisation

Answer 15

1. blood tests - for specific ige antibodies to allergen of interest
2. skin prick test

Question 16

how to test for eosinophilia

Answer 16

blood test during stable disease for eosinophil count
look at airways - use sputum
exhaled nitric oxide

Question 17

what is the exhaled nitric oxide test

Answer 17

non invasive biomarker of airway inflammation

good for measuring adherence and steroid response

Question 18

how to diagnose asthma using nice

Answer 18

history
examination
assess - wheeze
airway obstruction on spirometry <0.7 fev1:fvc
bronchodilator reversibility > 12%
exhaled no >35 ppb children
>40 ppb adults

Question 19

how to manage asthma

Answer 19

reduce eosinophilic inflammation - inhaled corticosteroids and leukotriene receptor agonists
acute symptomatic relief - beta 2 agonist, anticholinergic therapy
severe asthma - biologics targeted to ige and eosinophils (il5)

Question 20

what is role of corticosteroids in asthma management

Answer 20

prime function - reduce eosinophilia by promoting apoptosis
reduce type2 mediators
reduce mast cell numbers
can also impact structural cells?

Question 21

what is most important aspect of asthma management

Answer 21

optimal device and technique
clear asthma management plan
adherence to inhaled corticosteroids

Question 22

what happens during acute asthma attack

Answer 22

reduced antiviral responses - ifn alpha,beta and gamma reduced
reduced peak flow expiratory flow
increased airway eosinophilic inflammation

Question 23

what can cause acute asthma attack

Answer 23

combination of allergen
pathogens
pollution
and tobacco smoke

Question 24

what can be given to those who dont respond to high doses of ics

Answer 24

humanised anti igE antibodies
binds to IgE - prevents interaction with mast cells and basophils to stop allergic cascade
= reduction in serum igE

Question 25

what is omalizumab

Answer 25

anti IgE antiobody medication

Question 26

when can omalizumab be given

Answer 26

for severe persistent allergic asthma in patients >6years
have to have had frequent exacerbation
not responding to good adherence of corticosteroids
2-4 sc injections
igE outside 30-1500
dosing based on weight

Question 27

cons of omalizumab

Answer 27

quite expensive

Question 28

what is mepolizumab

Answer 28

anti il5 antibody

stops eosinophil recruitment

Question 29

when is mepolizumab recommended

Answer 29

at least 4 attacks in last year
for severe eosinophilic asthma
>300 eosinophils
trial for 12 months

eneed 50% red in exacerbation to continue

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