5.6 Asthma And Respiratory Immunology Flashcards
What are the cardinal features of asthma?
Wheeze with/without dry cough - on exertion, worse with colds or allergen exposure
Atopy (allergen sensitisation)
Reversible airflow obstruction
Airway inflammation (eosinophilia, type 2 lymphocytes)
What does an asthmatic airway wall look like?
Wall inflamed and thickened (eosinophil inflammation)
Narrowed airway lumen (turbulent air movement = wheeze)
What does an asthmatic airway wall look like during an attack?
Tightened smooth muscle
Wall inflamed and thickened (due to eosinophilia)
How do we test for asthma?
Spirometry (with nose clips)
What remodelling would we see in someone with asthma?
Increased smooth muscle number and size
Presence of eosinophils
Increased goblet cells in epithelium (produce mucus)
What do only some people get asthma?
Underlying genetic susceptibility
Then plus environmental exposure
= Asthma
What are some environmental exposures that could cause asthma?
Allergen
Infection
Pollution
I’m allergic asthma we see the increased expression of which IL cells?
4, 5, 13
What does IL-5 do in asthma?
Recruit eosinophils to the airway
What does IL4 do in asthma?
IgE synthesis
What does IL13 do in asthma?
Mucus secretion
What is the mechanism of asthma?
Exposed to allergen (inhaled)
Antigen presented to dentritic cells in lungs (antigen presenting cells)
They carry the antigen via MHC class 2 to the mediastinal lymph nodes
Where naive t helper cells (TH0) differentiate into TH2 cells
Which subsequently secretes the cytokines (IL4, 5, 13)
What happens when the patient is exposed to the antigen again
They will build an allergic immune response
Allergen is recognised by IgE
IgE then binds to mast cells
GFs, cytokines, chemokines release which is the allergic response to asthma
What type of hypersensitivity is allergic asthma?
Type 1 hypersensitivity
How do we test allergic sensitisation?
Blood test for IgE antibodies to allergens of interest (can’t just look for IgE alone)
Look for wheal and flare response in prick tests
How do we look for eosinophilia?
Blood test when stable (not during attack) > 300 cells/ mcl
Induced sputum eosinophil count >2.5%
Exhaled nitric oxide
What is exhaled nitric oxide?
Breath test,
Non invasive
Indirect maker of eosinophilic airway inflammation in asthma
What can exhaled nitric oxide be used for (FeNO)?
Asthma diagnosis
Assessing adherence to inhaled corticosteroids
What type of inflammation is allergic asthma?
Type 2
What exhaled nitric oxide would indicate poor adherence to corticosteroid inhaler?
High
What is the benefit of FeNO?
Easier for children
Non invasive
What should we look for in the blood when diagnosing allergic asthma?
eosinophil levels
Serum IgE
What are the 3 test we should do when diagnosing asthma?
(First confirm wheeze)
- Airway obstruction on spirometry <0.7
- Reversible airway obstruction - bronchodilator reversibility >12%
- Exhaled nitric oxide >35 ppb (children) , >40ppb (adults)
At least 2 out of 3
2. Needs to show variability so can do peak flow for 2 weeks instead
How do we manage asthma?
- Reduce airway eosinophilic inflammation
- Acute symptomatic relief
- Severe asthma - steroid sparing therapies
What does reduce airway eosinophilic inflammation involve?
Inhaled corticosteroids
Leukotriene receptor antagonists
What does acute symptomatic relief involve?
Beta 2 agonists (smooth muscle relaxation) Anticholinergic therapies (smooth muscle relaxation)
When are steroid sparing therapies used?
Very sever asthma
What are steroid sparing therapies?
Biologics targeted to IgE
- Anti- IgE antibody
Biological targeted to airway eosinophils
- Anti-interleukin 5 antibody
- Anti- interleukin 5 receptor antibody
Why do we use inhaled corticosteroids?
Reduce eosinophils
Reduce mast cell numbers
Reduce mucus secretion
Targets and reduced type 2 inflammation
What is the most important aspect of asthma management?
Optimal device and technique
Clear asthma management plan
Adherence to inhaled corticosteroids
What is prescribed first, preventer or acute relief?
Preventer first, cannot prescribe bronchodilator alone
What happens during an acute asthma attack?
If illness related; reduced anti viral response (by interferons) and increased viral replication, resulting in prolonged illness.
Reduced peak exploratory flow rate and increased airway obstruction resulting in acute wheeze (responsive to bronchodilators)
Increased airway eosinophilic inflammation (responsive to corticosteroids)
What can cause an acute asthma attack?
Many factors culminating in an event. Allergens Pathogens (virus or bacteria) Pollution Tobacco smoke
How do we treat an acute asthma attack?
High dose systemic steroid (prednisolone)
Why do we need steroid sparing treatment?
Some asthma doesn’t respond to steroid so we need to find another way to reduce attacks
What is Anti-IgE antibody therapy?
Humanised anti IgE monoclonal antibody
Binds and captures circulating IgE to prevent interaction with mast cells and basophils to stop allergic cascade
What does anti IgE cause?
Decrease in IgE over time
But not long term solution —> doesn’t cure (stopping results in symptoms returning in a few months)
What is the anti IgE antibody called?
Omulizimab
Who can use antibIgE antibodies as treatment for asthma?
Severe persistent allergic ( IgE mediated) asthma in patients >6 years old who need continuous or frequent treatment with oral corticosteroids ( 4 or more in previous year)
Have had optimised standard therapy
Documented compliance ( as very expensive!!)
What IgE level do you have to have to be prescribed anti IgE antibody?
Serum IgE 30-1500
How if anti - IgE antibody administered?
Dosing based on weight and serum IgE
Subcutaneous injections 2-4x weekly
What is the anti-IL5 antibody called?
Mepolizumab
When is anti IL5 antibody prescribed
For severe eosinophilic asthma
Blood eosinophils >300 cells/mcl in last 12 months
At least 4 exacerbations requiring oral steroids in last 12 months
For adults and children more than 6
Trial for 12 months - if 50% reduction in attacks then continue
What does IL5 do?
Regulates growth, recruitment, activation and eosinophil survival
How do we know anti IL5 antibodies work as eosinophilic asthma treatment (clinically significant at reducing exacerbations)
DREAM study
