Asthma

Question 1

Describe the epidemiology of asthma in the UK?

Answer 1

5.4 Mill getting treatment

3 people die of asthma attack every day in the UK

Costs NHS 1 billion annully

Question 2

What are the cardinal features of asthma?

Answer 2

Wheeze +/- dry cough on exertion

Worse with colds and allergen exposure

Atopy/allergy sensitisation

Airway inflammation:

• Eosinophilia
• Type 2 lymphocytes

Question 3

Describe the pathphysiology of asthma?

Answer 3

Reversible airflow obstruction

Airway Eosinophilia

Compared to normal airways, asthma px will have inflamed thicker walls and DURING attack the smooth muscles are tightened and air gets trapped in alveoli

• with treatment the ‘normal’ asthma px airways should look like a healthy persons

Question 4

Describe the pathogenesis of allergic asthma? * how does pollen cause a thicker airway and asthma development

Answer 4

–> Pollen/dustmites/mold

–> bronchial epithelium inflammation

–> airway remodelling ( changes in structural cells e.g. inflammatory cells - eosinophils and changes in epithelium with increased goblet cells, matrix increases and size of smooth muscle cells increase ) = ticker airway wall

Question 5

Why do not all people who have been allergen sensitized develop asthma?

Answer 5

Genetic susceptibility is a key aspect

If then the environment exposures to an allergen

• It may cause allergy
• Inflammation
• Or reversible airway obstruction

Question 6

Which gene may lead to genetic suceptibility?

Answer 6

GSDMB

IL33

• these genes are over expressed in those with asthma

Question 7

Why is type II immunity important in allergic asthma?

Answer 7

Determines which test you do

Question 8

How does Type II immunity work in asthma?

Answer 8

Exposed to antigen from allergen

presented to APC - Dendtritic cells in lungs

carries antigen to lymph nodes with MHC class II

Where naive T helper cells differentiate into Th2 cells

These release IL-4 IL-5 IL-13

Question 9

What does IL-5 do?

Answer 9

Recruit eosinophils in airways and promotes survival

Question 10

What does IL-4

Answer 10

convert plasma cells to secrete IgE

Question 11

What does IL-13 do?

Answer 11

Mucous secretion

Question 12

What tests are done for allergic sensitization?

Answer 12

Blood tests : for specific IgE antibodies to allergens of interest

Total IgE alone is not sufficient to define atopy

Question 13

What tests are done for Eosinophilia?

Answer 13

• Blood count : When blood is stable but
  eosinophils are >300ml
• Induced sputum eosinophil count >2.5% is abnormal
• breath taste - exhaled nitric oxide

Question 14

How to do a skin prick test for allergies?

Answer 14

Intradermal injection of positive control HISTAMINE as we all react to that

and negative control of saline

Then test with allergens

Measure size of wheel

Question 15

What in an example of a non-invasive biomarker of airways type 2 inflammation?

Answer 15

Fraction of exhaled Nitric Oxide (FeNO)

it is quantitative, safe, non invasive

Indirect marker of T2 high eosinophilic airway inflammation

• provided they are not on treatment with steroids, this can be a diagnostic tool for asthma

Will know if someone is or not taking their steroid treatment

Question 16

What tests are done to diagnose asthma clinically?

Answer 16

Conform presence of wheeze when unwell during history

Look for:

• Airway obstruction on spirometry - FEV1/FVC ration <0.7
• Reversible airway obstruction - Bronchodilator reversibility >12%
• Exhaled nitric oxide (FeNO) >35ppb (children), >40ppb (adults)

Question 17

What are the NICE guidelines for diagnosis?

Answer 17

have symptoms AND

FeNO levels of 35ppb + and positive peak flow variability

OR

obstructive spirometry and positive bronchodilator reversibility

Question 18

How is asthma managed?

Answer 18

Reduce eosinophilic inflammation

acute symptomatic relief

if severe - steroid sparing therpaies

Question 19

What treatments are available for reduction of airway eosinophilic inflammation?

Answer 19

Inhaled corticosteroids (ICS)
Leukotriene receptor antagonists

Question 20

What acute symptomatic relief treatments are there ?

Answer 20

Beta-2 agonists (smooth muscle relaxation)
Anticholinergic therapies (smooth muscle relaxation)

• dangerous to give often and definately not without inflammation therapy. need to do together

Question 21

What steroid sparing therapies are there?

Answer 21

Biologic targeted to IgE
Anti-IgE antibody
Biologics targeted to airway eosinophils
Anti-interleukin-5 antibody
Anti-interleukin-5 receptor antibody

Question 22

Whats the function o cotricosteoid?

Answer 22

targe type 2 inflammation

Apoptosis of lower eosinophils

Reduce mast cells

can impact structural cells + remodelling

Question 23

What basics need to be told to the px?

Answer 23

Must make sure they are taking their inhaled corticosteroid preventor treatments

optimial device and technique

clear asthma management plan

Question 24

what leads to an asthma attack?

Answer 24

Allergens + pathogens + pollution + tobacco smoke can all cause changes to epithelium. Multiple events come together results in an asthma attack

Question 25

Why does infection to those with asthma result in asthma attack?

Answer 25

Those with asthma will have lower IFN- a so reduced anti viral replication result in a prolonged illness

Question 26

What will a peak flow look like of a px with asthma attack?

Answer 26

reduced peak expiratory flow rate

increased airway obstruction

acute wheeze

responsive to bronchodilators

Question 27

What is Anti-IgE antibody therpay?

Answer 27

For those who are not responding to steroids

this antibody can capture circulating IgE to prevent mast cell interaction and basophils to stop allergic cascade

over time this lowers IgE production over time

• no evidence that asthma will go away if treatment is stopped

Question 28

What is Omalizumab?

Answer 28

The Anti-IgE antibody that is being used

For those with frequent attacks, over 6 years

with documented compliance

Question 29

What is an issue with omalizumb?

Answer 29

fixed serum IgE level for which it can be prescribed - 30-1500

given as injections depending on levels and weight, quite expensive

Question 30

What is Mepolizumab?

Answer 30

Anti IL5-antibody

for severe eosinophilic asthma, over 6+

stops eosinophil recruitment

if eosiniphils >300 cells/mcl

at least 4 exacerbation which required oral steroids in the last 12 months

need 50% reduction in attacks to continue