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BRS 1b > 5.6 Asthma And Respiratory Immunology > Flashcards

5.6 Asthma And Respiratory Immunology Flashcards

1
Q

What are the cardinal features of asthma?

A

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)

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2
Q

What does an asthmatic airway wall look like?

A

Wall inflamed and thickened (eosinophil inflammation)

Narrowed airway lumen (turbulent air movement = wheeze)

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3
Q

What does an asthmatic airway wall look like during an attack?

A

Tightened smooth muscle

Wall inflamed and thickened (due to eosinophilia)

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4
Q

How do we test for asthma?

A

Spirometry (with nose clips)

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5
Q

What remodelling would we see in someone with asthma?

A

Increased smooth muscle number and size
Presence of eosinophils
Increased goblet cells in epithelium (produce mucus)

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6
Q

What do only some people get asthma?

A

Underlying genetic susceptibility
Then plus environmental exposure
= Asthma

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7
Q

What are some environmental exposures that could cause asthma?

A

Allergen
Infection
Pollution

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8
Q

I’m allergic asthma we see the increased expression of which IL cells?

A

4, 5, 13

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9
Q

What does IL-5 do in asthma?

A

Recruit eosinophils to the airway

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10
Q

What does IL4 do in asthma?

A

IgE synthesis

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11
Q

What does IL13 do in asthma?

A

Mucus secretion

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12
Q

What is the mechanism of asthma?

A

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)

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13
Q

What happens when the patient is exposed to the antigen again

A

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

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14
Q

What type of hypersensitivity is allergic asthma?

A

Type 1 hypersensitivity

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15
Q

How do we test allergic sensitisation?

A

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

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16
Q

How do we look for eosinophilia?

A

Blood test when stable (not during attack) > 300 cells/ mcl
Induced sputum eosinophil count >2.5%
Exhaled nitric oxide

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17
Q

What is exhaled nitric oxide?

A

Breath test,
Non invasive
Indirect maker of eosinophilic airway inflammation in asthma

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18
Q

What can exhaled nitric oxide be used for (FeNO)?

A

Asthma diagnosis

Assessing adherence to inhaled corticosteroids

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19
Q

What type of inflammation is allergic asthma?

A

Type 2

20
Q

What exhaled nitric oxide would indicate poor adherence to corticosteroid inhaler?

A

High

21
Q

What is the benefit of FeNO?

A

Easier for children

Non invasive

22
Q

What should we look for in the blood when diagnosing allergic asthma?

A

eosinophil levels

Serum IgE

23
Q

What are the 3 test we should do when diagnosing asthma?

A

(First confirm wheeze)

  1. Airway obstruction on spirometry <0.7
  2. Reversible airway obstruction - bronchodilator reversibility >12%
  3. 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

24
Q

How do we manage asthma?

A
  1. Reduce airway eosinophilic inflammation
  2. Acute symptomatic relief
  3. Severe asthma - steroid sparing therapies
25
Q

What does reduce airway eosinophilic inflammation involve?

A

Inhaled corticosteroids

Leukotriene receptor antagonists

26
Q

What does acute symptomatic relief involve?

A 
Beta 2 agonists (smooth muscle relaxation)
Anticholinergic therapies (smooth muscle relaxation)
27
Q

When are steroid sparing therapies used?

A

Very sever asthma

28
Q

What are steroid sparing therapies?

A

Biologics targeted to IgE
- Anti- IgE antibody

Biological targeted to airway eosinophils

  • Anti-interleukin 5 antibody
  • Anti- interleukin 5 receptor antibody
29
Q

Why do we use inhaled corticosteroids?

A

Reduce eosinophils
Reduce mast cell numbers
Reduce mucus secretion
Targets and reduced type 2 inflammation

30
Q

What is the most important aspect of asthma management?

A

Optimal device and technique
Clear asthma management plan
Adherence to inhaled corticosteroids

31
Q

What is prescribed first, preventer or acute relief?

A

Preventer first, cannot prescribe bronchodilator alone

32
Q

What happens during an acute asthma attack?

A

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)

33
Q

What can cause an acute asthma attack?

A 
Many factors culminating in an event.
Allergens
Pathogens (virus or bacteria)
Pollution 
Tobacco smoke
34
Q

How do we treat an acute asthma attack?

A

High dose systemic steroid (prednisolone)

35
Q

Why do we need steroid sparing treatment?

A

Some asthma doesn’t respond to steroid so we need to find another way to reduce attacks

36
Q

What is Anti-IgE antibody therapy?

A

Humanised anti IgE monoclonal antibody

Binds and captures circulating IgE to prevent interaction with mast cells and basophils to stop allergic cascade

37
Q

What does anti IgE cause?

A

Decrease in IgE over time

But not long term solution —> doesn’t cure (stopping results in symptoms returning in a few months)

38
Q

What is the anti IgE antibody called?

A

Omulizimab

39
Q

Who can use antibIgE antibodies as treatment for asthma?

A

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!!)

40
Q

What IgE level do you have to have to be prescribed anti IgE antibody?

A

Serum IgE 30-1500

41
Q

How if anti - IgE antibody administered?

A

Dosing based on weight and serum IgE

Subcutaneous injections 2-4x weekly

42
Q

What is the anti-IL5 antibody called?

A

Mepolizumab

43
Q

When is anti IL5 antibody prescribed

A

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

44
Q

What does IL5 do?

A

Regulates growth, recruitment, activation and eosinophil survival

45
Q

How do we know anti IL5 antibodies work as eosinophilic asthma treatment (clinically significant at reducing exacerbations)

A

DREAM study

BRS 1b (25 decks)

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