asthma and respiratory immunology Flashcards
epidemiology of asthma in uk
5.4 mill people currently receiving treatment
1.1 mill children affected
3 people die of asthma a day
nhs spends 1 bill annually
what are the cardinal features of asthma
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
what is the pathophysiology of asthma
thickened airway wall caused by inflammation
increase in airway smooth muscle
airway lumen narrowed
what causes wheezing
airways narrowed - causes turbulent flow
how can we look for reversible airway obstruction
most common lung function test is spirometry
what mostly causes airway inflammation
eosinophils
why are nose clips worn during spirometry
so exhalation is just through mouth
what is the pathogenesis of allergic asthma
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
why are only some who are sensitised develop asthma
genetic susceptibility
with environmental exposure leads to airflow obstruction
how do we know that asthma involved genetic susceptibilty
genome wide association studies e.g il1r1 rad50 il33 ! gsdmb !
asthma is a multi gene disorder
describe type 2 immunity in allergic asthma
antigen binds to mhc2 on apc
th0 differentiate to th2 and th1
th2 secretes 1l4,5,13
results in allergic reaction - histamines,mediators…
what is role of il5
recruits eosinophils in airways and promotes eosinophil survival
what is role of il4
helps conversion of b cells/ plasma cells to secrete ige
what is il 13 involved in
mucus secretion
how to look for evidence of allergen sensitisation
- blood tests - for specific ige antibodies to allergen of interest
- skin prick test
how to test for eosinophilia
blood test during stable disease for eosinophil count
look at airways - use sputum
exhaled nitric oxide
what is the exhaled nitric oxide test
non invasive biomarker of airway inflammation
good for measuring adherence and steroid response
how to diagnose asthma using nice
history examination assess - wheeze airway obstruction on spirometry <0.7 fev1:fvc bronchodilator reversibility > 12% exhaled no >35 ppb children >40 ppb adults
how to manage asthma
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)
what is role of corticosteroids in asthma management
prime function - reduce eosinophilia by promoting apoptosis
reduce type2 mediators
reduce mast cell numbers
can also impact structural cells?
what is most important aspect of asthma management
optimal device and technique
clear asthma management plan
adherence to inhaled corticosteroids
what happens during acute asthma attack
reduced antiviral responses - ifn alpha,beta and gamma reduced
reduced peak flow expiratory flow
increased airway eosinophilic inflammation
what can cause acute asthma attack
combination of allergen
pathogens
pollution
and tobacco smoke
what can be given to those who dont respond to high doses of ics
humanised anti igE antibodies
binds to IgE - prevents interaction with mast cells and basophils to stop allergic cascade
= reduction in serum igE
what is omalizumab
anti IgE antiobody medication
when can omalizumab be given
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
cons of omalizumab
quite expensive
what is mepolizumab
anti il5 antibody
stops eosinophil recruitment
when is mepolizumab recommended
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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