Asthma And Respiratory Immunology

Question 1

cardinal features of asthma?

Answer 1

wheeze ± dry cough ± dyspnoea

allergen sensitisation/atopy

reversible airway obstruction

eosinophilic airway inflammation

Question 2

What can cause inflammation

Answer 2

Eosinophilia
Th2 lymphocytes (cd4 cells)

Question 3

Disease progression pattern

Answer 3

Persistent symptoms and attacks

Question 4

What can precipitate attacks

Answer 4

Exertion,cold,allergen exposure

Question 5

Features of flow volume loop

Answer 5

Indented teardrop shape,obstructive disorder
(Bottom of graph stays the same where inspiration occurs and top dents where expiration is occurring)
Fev1/fvc is <0.7 in adults and .8 in children

Question 6

Why’d doesn’t everyone exposed to the same allergen get asthma

Answer 6

Genetic susceptibility plays a role

Question 7

• what type of immune response dominates in allergic asthma?

Answer 7

type 2 → Th2 cells

Question 8

What do Th2 cells do

Answer 8

Increase IL-4,5,13
Which causes eosinophilic airway inflammation
IL-4 causes IgE release
IL-5 causes eosinophil release which releases histamines, cytokines
IL-13 causes mucus production

Question 9

How to test for allergic sensitisation

Answer 9

Skin tests,IgE blood tests for allergens of interest
Total IgE alone not sufficient to define atopy (diagnkse(

Question 10

How to test for eosinophilia

Answer 10

Stable blood eosinophils if 300 cells/mcl if more then it is abnormal
Exhaled nitric oxide
induced sputum eosinophil count >3%

Question 11

What is the relevance of nitric oxide

Answer 11

FeNO → fraction of exhaled nitric oxide

non-invasive indirect biomarker used to measure eosinophilic airway inflammation

can aid diagnosis and assess response to inhaled corticosteroids

Question 12

FeNO benchmarks

Answer 12

• childrenless than 15-20 normal15-20 to 35 likely Th235+ significant
• adults0 to 20-25 normal20-25 to 50 likely Th250+ significant

Question 13

Asthma diagnostic investigations

Answer 13

clinical assessment → history and exam, wheeze when acutely unwell

tests →

FEV1/FVC ratio less than 0.7 in adults, 0.8 in children (obstructive disorder)

bronchodilator reversibility 12+ % (reversible airway obstruction)

FeNO > 35 in children, > 40 in adults (pre-treatment)

Question 14

Criteria for diagnosis ages 5-16

Answer 14

Symptoms and peak flow variability
FeNO 35+ and peak flow variability or obstructive spirometry and positive bronchodilator reversibility

Question 15

How is airway inflammation decreased

Answer 15

Inhaled corticosteroids
Leukotriene receptor agonist

Question 16

Acute symptomatic relief

Answer 16

Beta 2 agonists
Anticholinergic therapies
Both smooth muscle relaxants

Question 17

Severe asthma cases

Answer 17

Biologic vs IgE
Biologic vs IL5 antibody and and receptor antibody
Biologics vs IL-4 AND IL-13 (anti interleukin 4Ra antibody)
Both so are steroid use

Question 18

how do corticosteroids help?

Answer 18

reduce immune cell numbers and cytokines including eosinophils

less mucus, more beta-2 receptors on smooth muscle, less leak in endothelial cells

Question 19

typical treatment options (increasing severity)?

Answer 19

low dose inhaled corticosteroids at first

add on either long-acting beta agonists or leukotriene receptor antagonists (esp for young children)

add on other option, increase corticosteroid dose

refer for specialist care

short acting beta 2 agonists as required

Question 20

approaches to improving adherence?+ single inhaler maintenance and reliever therapy

Answer 20

clear plan, right equipment

SMART → single inhaler combination dose of ICS and LABA → can be used for regular maintenance or relief dose

reduces total delivered dose of ICS

Question 21

significance of interferons alpha, beta, gamma?

Answer 21

reduced in asthma pathophysiology → susceptibility to virus → more triggers for asthma

Question 22

example of an anti-IgE antibody?

Answer 22

omalizumab → monoclonal antibody

Question 23

When is omalizumab given

Answer 23

Severe persistent allergic asthma,patient 6+ years old,documented compliance,required frequent (4+ courses in last year) of corticosteroid treatment
total serum IgE of 30-1500IU/ml
dose based on weight and serum ige levels
given as subcutaneous injections

Question 24

what antibody can be used for severe eosinophilic asthma?

Answer 24

anti-IL5 antibody → mepolizumab
IL-5 regulates growth recruitment activation and eosinophil survival

Question 25

When is mepolizumab given

Answer 25

6+ years old, severe eosinophilic asthma

blood eosinophils 300+ in last year

4+ exacerbations requiring corticosteroids in last year

12 month trial and continue if 50% reduction in attacks

Question 26

alternative monoclonal antibody?

Answer 26

dupilumab → vs shared receptor for IL-4, IL-13

Question 27

treatment outcomes?

Answer 27

fewer asthma attacks, improved lung function

Question 28

what kind of airflow occurs

Answer 28

turbulent which causes the wheeze

Question 29

pathogenesis of allergic asthma

Answer 29

In asthma, the bronchial epithelium becomes damaged and more permeable, allowing allergens to enter and trigger inflammation. This damage leads to the release of cytokines such as IL-4, IL-5, and IL-13, which drive the inflammatory response. These cytokines stimulate smooth muscle contraction around the airways, leading to bronchoconstriction, while also promoting extracellular matrix (ECM) remodeling with increased collagen deposition, which narrows the airways over time. Additionally, eosinophils are recruited to the site and release toxic granules, further exacerbating inflammation and contributing to chronic airway remodeling.

Question 30

upper airway fixed obstruction

Answer 30

endotracheal tumour
large airway foreign body

Question 31

anti IgE antibody therapy

Answer 31

humanised anti ige antibody
binds and captures circulating ige to prevent interaction with mast cells and basophils prevetning allergic cascade
ige production decreases with time