Asthma and Respiratory Immunology Flashcards
What are the cardinal features of asthma?
Wheeze +/- Dry cough - on exertion, worse w/ colds/ allergen exposure
Atopy / allergen sensitisation
Reversible airflow obstruction
Airway inflammation (Eosinophilia, type 2 - lymphocytes)
Draw a flow volume loop for reversible airflow obstruction.
PPT1 SLIDE 6
Compare asthmatic airway and asthmatic airway during attack.
asthmatic: relaxed smooth muscle, wall inflamed/thickened, mucus, asthmatic under attack: air trapped in alveoli, tightened smooth muscles, wall inflamed/thickened, mucus
Pathogenesis of allergic asthma
allergen > inflammation/airway remodelling > thick matrix, increased immune cell recruitment
Why do only some people who are sensitized develop disease (asthma)?
genetic susceptibility
environmental exposures
Briefly outline type 2 immunity in allergic asthma.
antigen > MHC II (APC) > Th0 > Th2>
- > IL-5 > eosinophilic airway inflammation
- > IL-4, IL-13 > VCAM-1 expression, mast cell proliferation, IgE synthesis, mucin secretion
Tests for allergic sensitization
Blood tests – for specific IgE antibodies to allergens of interest
Total IgE alone not sufficient to define atopy
Tests for eosinophilia
Blood eosinophil count when stable: >300 cells /mcl is abnormal
Induced sputum eosinophil count: >2.5% eosinophils is abnormal
Exhaled nitric oxide
What is a method of measuring airway inflammation?
fractional concentration of exhaled nitric oxide
Benefits to FeNO
quantitative
safe
non invasive
Role of FeNO
aiding asthma diagnosis
predicting steroid responsiveness
assessing adherence to inhaled corticosteroids
FeNO is an indirect marker of what?
T2 high eosinophilic airway inflammation in asthma
NICE asthma clinical assessment guidelines
history + examination
assess/confirm wheeze when acutely unwell
NICE asthma objective tests diagnosis guidelines
Airway obstruction on spirometry - FEV1/FVC ration <0.7
Reversible airway obstruction - Bronchodilator reversibility >12%
Exhaled nitric oxide
Diagnose asthma in children and young people (aged 5to16) if they have symptoms suggestive of asthma and?
FeNO level >35ppb + +ve peak flow variabilityor obstructive spirometry + +ve bronchodilator reversibility
Management of asthma includes?
reduce airway eosinophilic inflammation, acute symptomatic relief, severe asthma - steroid sparing therapies
How to reduce airway eosinophilic inflammation?
inhaled corticosteroids
leukotriene receptor antagonists
How to achieve acute symptomatic relief for asthma?
beta-2 agonists anticholinergic therapies
both for smooth muscle relaxation
What are steroid sparing therapies for management of severe asthma?
biologic targeted to IgE (anti IgE antibody)
biologics targeted to airway eosinophils
Anti-IL-5 antibody
Anti-IL-5 receptor antibody
Corticosteroids work on what inflammatory cells?
eosinophils t-lymphocytes mast cells macrophages dendritic cell
Corticosteroids work on what structural cells?
epithelial
endothelial
airway smooth muscle
mucus gland
What effect do corticosteroids have on inflammatory cells?
reduce their numbers
reduce their cytokines
What effect do corticosteroids have on structural cells?
decrease mucus, mediator, cytokine production
decrease leakage from endothelial cells
upregulates B2 receptors on smooth muscle
What are the most important aspect of asthma management?
optimal device and technique
clear management plan
adherence to inhaled corticosteroids
Average adherence to ICS?
33%
Pathogenesis of acute asthma attack?
allergens/pathogens/pollution/tobacco smoke > increased airway eosinophilic inflammation, reduced IFN anti viral response
What is anti-IgE antibody therapy for?
Binds and captures circulating IgE – to prevent interaction with mast cells and basophils to stop allergic cascade
How can IgE production change with anti-IgE antibody therapy over time?
IgE production can decrease > therapy may not need to be used indefinitely
What is Omalizumab?
anti-IgE antibody
What is Mepolizumab?
anti-IL5-antibody
Current UK recommendations for omalizumab?
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
Omalizumab dosing is based on?
weight
serum IgE
IL-5 regulates what?
growth, recruitment, activation, eosinophil survival
Current UK recommendations for mepolizumab
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
