Asthma and Respiratory Immunology Flashcards
What is asthma?
“Reversible airflow obstruction” (problem with expiration not inspiration)
- Airways become inflamed, narrow and mucus is produced
What are the cardinal features of asthma?
- Wheeze +/- Dry cough +/- Dyspnoea
- Persistent symptoms + episodes (attacks) worsened by:
* exertion
* colds
* allergen exposure - Atopy / allergen sensitisation
- Reversible airflow obstruction
- Airway inflammation:
* Eosinophilia
* Type 2 - lymphocytes
What is atopy?
Atopy is a predisposition to an immune response against diverse antigens and allergens
Describe the pathophysiology of asthma
- Allergen/ trigger in environment
- Picked up by APC cells on their MHC II
- The APC activates Th2 cells
- Th2 proliferate and produce the cytokines: IL-4= activation of B cells that release IgE, IL-5= increases eosinophil numbers (inflammation), IL-13= production of mucus
What is the role of IgE in asthma?
- IgE antibodies respond- bind to mast cells and basophils
- Mast cells released cytokines (histamine)
- These cytokines contract the smooth muscle around airways= airway tightening
What are the main 3 targeted interleukins in asthma? what do they do?
IL-4: activation of B cells that released IgE
IL-5: Increases eosinophil numbers
IL-13: production of mucus
What do only some people who are sensitized develop disease (asthma)?
There has to be some genetic susceptibility (+ the environmental exposure) causing asthma
Which genes are associated with asthma?
We don’t know what genes cause it, but studies show the genes:
IL-33 and GSDMB
are v. specifically associated with asthma
How is asthma diagnosed?
Invasive tests:
1. test for allergic sensitisation
2. Test for eosinophilia
and non-invasive tests:
1. Spirometry
2. Fractional exhaled nitric oxide (FeNO- this also tests for eosinophilia)
How do you test for allergic sensitization in asthma?
Blood tests – for specific IgE antibodies to allergens of interest
Total IgE alone not sufficient to define atopy
How do you test for eosinophilia?
- Blood eosinophil count: when stable: >300 cells/mcl is abnormal (in a patient with suspected/confirmed asthma)
- Induced sputum eosinophil count: >3% eosinophils is abnormal
- Exhaled nitric oxide
What is Fraction of exhaled nitric oxide (FeNO)? how does it help diagnose asthma?
Fractional concentration of exhaled nitric oxide (FeNO) is a quantitative, non-invasive and safe method of measuring airway inflammation:
- Nitric oxide is produced in large amounts in inflammatory cells esp eosinophils
what is spirometry?
- Clips placed on patients nose
- Patient inhales fully, so the lungs are completely filled with air
- Patient closes their lips tightly around the mouthpiece
- Exhale as quickly and forcefully as they can, making sure they empty the lungs fully
How does spirometry help diagnose asthma?
- In asthma, spirometry will show reduced flow on EXPIRATION: ability to breathe out quickly is affected by narrowing of the airways, but the amount of air you can hold in your lungs is normal (inspiration unaffected)
- FEV1 is significantly reduced but FVC is normal
- so the FEV1/FVC ratio is reduced (<70%)
What is the criteria to diagnose asthma in children 0-5?
Clinical judgement basis alone
What is the criteria to diagnose asthma in children 5-16?
Symptoms AND:
- spirometry with bronchodilator reversibility
OR
Symptoms AND:
- FeNO test level of 35 ppb or more and positive peak flow variability
(don’t need both)
What is the criteria to diagnose asthma in adults?
Symptoms AND:
Spirometry with bronchodilator reversibility AND FeNO test level of 40 ppb
(both tests need to be positive)
Why do you need both spirometry and FeNO to be positive to diagnose asthma in adults, but only 1 for children?
Adults may have reduced lung function due to age; spirometry readings could be lowered but still normal (not asthma)
But in children, lung function should be normal
What is the general management process/ order for asthma?
- Reduce airway eosinophilic inflammation
- Inhaled corticosteroids (ICS)
- Leukotriene receptor antagonists - Acute symptomatic relief
- Beta-2 agonists (smooth muscle relaxation)
- Anticholinergic therapies (smooth muscle relaxation) - Severe asthma – steroid sparing therapies
- Biologic targeted to IgE:
* Anti-IgE antibody
- Biologics targeted to airway eosinophils:
* Anti-interleukin-5 antibody
* Anti-interleukin-5 receptor antibody
Describe the mechanism of action of Inhaled corticosteroids in the treatment of asthma
“dampen airway eosinophilia”:
1. Reduced recruitment of eosinophils
2. Steroids stimulate apoptosis of eosinophils
Describe the mechanism of action of Leukotriene receptor antagonist in the treatment of asthma?
Can reduce eosinophilic inflammation
Describe the mechanism of action of beta-2 agonists in the treatment of asthma?
SABA- short acting beta- 2 agonist (e.g. salbutamol)
LABA- Long acting beta- 2 agonist (e.g. salmeterol)
both= symptom relief
What are the 3 important things you need to check before perscribing biologics?
Biologics are a final line treatment (ICS, LTRA’s and beta-2 agonists should all be considered first)
Before prescribing further medications, check:
1. Optimal device and technique
2. Clear asthma management plan
3. Adherence to inhaled corticosteroids
Describe the mechanism of action of biologics in the treatment of asthma
- Omalizumab: Anti IgE antibody
- Humanised anti-IgE monoclonal antibody
- Binds and captures circulating IgE – to prevent interaction with mast cells and basophils to stop allergic cascade - Mepolizumab: Anti-IL-5 antibody
- IL-5 regulates growth, recruitment, activation and eosinophil survival
Biologics are rarely used and only once most other options have been tried and tested.
