Asthma

Question 1

what are the cardinal features of asthma?

Answer 1

wheeze +/- dry cough
atopy
reversible airflow obstruction
airway inflammation - eosinophilia, type 2 lymphocytes

Question 2

what is the structure of an asthmatic airway?

Answer 2

thickened airway wall, inflammation
eosinophil infiltration
increased goblet cells
increased matrix
hypertrophy and hyperplasia of smooth muscle

Question 3

how does an asthmatic airway change during an acute attack?

Answer 3

smooth muscle contracts, air gets trapped in alveoli

wall becomes more inflamed

Question 4

how does type 2 hypersensitivity/immunity work in asthma?

Answer 4

allergens attach to MHC class II on APCs
presented to Th0 cells
Th2 cells produce IL-4,5,13 
inititated eosinophilic airway inflammation, IgE synthesis, mast cell proliferation, mucin secretion and VCAM-1 expression
mast cells and eosinophils degranulate

Question 5

what is IL-4 responsible for?

Answer 5

promotes plasma cells to produce IgE

Question 6

what is IL-5 responsible for?

Answer 6

eosinophil recruitment

Question 7

what is IL-13 responsible for?

Answer 7

mucin secretion

Question 8

what are the tests for allergic sensitisation?

Answer 8

blood test for specific IgE antibodies to allergens of interest
allergy skin tests - wheal and flare reactions

Question 9

What are 3 tests for eosinophilia?

Answer 9

Blood eosinophil count when stable: =/> 300 cells/mcl is abnormal
Induced sputum eosinophil count: >/= 2.5% eosinophils is abnormal
Exhaled nitrous oxide

Question 10

how does exhaled nitric oxide help with eosinophil count?

Answer 10

indirect marker of T2-high eosinophilic airway inflammation in asthma

Question 11

when are exhaled nitric oxide tests used?

Answer 11

aiding diagnosis
predicting steroid responsiveness
assessing adherence to corticosteroids

Question 12

what is required for a full asthmatic diagnosis?

Answer 12

airway obstructive on spirometry - FEV1/FVC less than 0.7
=/>12% bronchodilator reversibility
exhaled NO - >35ppb in children, 40ppb in adults
assess/confirm wheeze when acutely unwell
history and examination

Question 13

when should you diagnose asthma in children/YA (5-16)?

Answer 13

symptoms of asthma AND
FeNO 35ppb+ and positive peak flow variability
OR obstructive spirometry and positive bronchodilator reversibility

Question 14

what medications should all asthmatic patients be prescribed?

Answer 14

maintenance anti-eosinophilics - inhaled corticosteroids, leukotriene receptor antagonists
acute symptomatic relief - beta-2-agonist, anticholinergic therapies

Question 15

what additional medications should patients with severe asthma be prescribed?

Answer 15

steroid sparing therapies- biologics against IgE (anti-IgE)

biologics targeted to airway eosinophils: anti- IL5 AB, anti-IL5 R AB

Question 16

what is the mechanism of action of corticosteroids?

Answer 16

decreases numbers of eosinophils, mast cells, dendritic cells
decreased cytokines by T lymphocytes, macrophages, epithelial cells
decreased mucus secretion
decreased endothelial cells leakage
decreased mediators and cytokines by airway smooth muscle
increased beta2 receptors on airway smooth muscle cells

Question 17

what are the most important aspects for asthma management?

Answer 17

optimal device and technique by patient
clear asthma management plan
adherence to inhaled corticosteroids

Question 18

what are each of the step-ups for adult asthma management escalation?

Answer 18

start on regular preventer - low dose ICS
initial add on - add inhaled LABA to low dose ICS
additional controllers - increased ICS to medium dose or adding LTRA (consider stopping LABA if no response)
specialist therapies - refer patient to specialist care

Question 19

what may trigger an acute lung attack in school age children?

Answer 19

allergens
pathogens
pollution
tobacco smoke

Question 20

what is an acute lung attack in school age children?

Answer 20

decreased IFN a,b,gamma (reduced viral responses)
reduced peak expiratory flow
eosinophilic inflammation

Question 21

what is omalizumab?

Answer 21

humanised anti-IgE monoclonal antibody
binds and captures IgE to prevent interaction with mast cells and basophils to stop allergic cascade
IgE production decreases with time as given anti-IgE AB

Question 22

what are the requirements for omalizumab prescription?

Answer 22

severe, persistent allergic asthma in 6+ yrs who need continuous or frequent treatment w oral corticosteroids
documented compliance (4 or more corses in prev year)
Total serum IgE between 30-1500
Given 2-4 weekly s/c injections

Question 23

what is mepolizumab?

Answer 23

anti IL-5 antibody
regulated growth, recruitment, activation and eosinophil survival
for children 6+ yrs

Question 24

what are the requirements for mepolizumab?

Answer 24

Severe eosinophilic asthma
Blood eosinophils >300cells/mcl in last year
At least 4 exacerbations requiring oral steroids in last year
6+ years old
trialed for 12 months- 50% reduction in attack then continue

Question 25

Why do only some people who are sensitised develop asthma?

Answer 25

Genetic susceptibility- allergy and allergic disease
Environmental exposures: allergen, infection, pollution
These lead to: allergy, reversible airflow obstruction and inflammation

Question 26

What genes are more prevalent is asthma?

Answer 26

IL-33

GSDMB

Question 27

How is a allergy skin test carried out?

Answer 27

Intradermal injection of allergen
In positive control: histamine
In negative control: saline
Wheal and flare reaction if allergic

Question 28

How can asthma medication adherence be checked?

Answer 28

Electric monitor to see if patient is taking meds

Question 29

what are each of the step-ups for paediatric asthma management escalation?

Answer 29

Regular preventer: very low dose ICS (or LTRA <5YRS)
Initial add-on therapy: very low does ICS plus children 5+ add inhaled LABA or LTRA, children <5 add LTRA
Additional controller therapies: Increase ICS dose or children 5+ add LTRA or LABA (if no response to laba stop it)
Specialist therapies: refer to specialist care