1b// 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
Th1 cells -> VCAM-1, mast cell proliferation, IgE synthesis + mucin secretion
Th2 cells -> IL4 (plasma cells becoming b-cells & secreting IgE), IL5 (eosinophilia), IL13 (mucus secretion)

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 the tests for eosinophilia?

Answer 9

blood eosinophil count
sputum eosinophil count
exhaled nitric oxide

Question 10

what eosinophil blood count indicated eosinophilia?

Answer 10

> including 300 cells/mcl

Question 11

what eosinophil sputum count is abnormal?

Answer 11

> including 2.5% eosinophils

Question 12

how does exhaled nitric oxide help with eosinophil count?

Answer 12

indirect marker of T2-high eosinophilic airway inflammation in asthma

Question 13

when are exhaled nitric oxide tests used?

Answer 13

aiding diagnosis
predicting steroid responsiveness
assessing adherence to corticosteroids

Question 14

what is required for a full asthmatic diagnosis?

Answer 14

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

Question 15

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

Answer 15

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

Question 16

what medications should all asthmatic patients be prescribed?

Answer 16

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

Question 17

what additional medications should patients with severe asthma be prescribed?

Answer 17

steroid sparing therapies- biologics against IgE or airway eosinophils

Question 18

what is the MOA of corticosteroids?

Answer 18

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 19

what are the most important aspects for asthma management?

Answer 19

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

Question 20

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

Answer 20

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 21

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

Answer 21

allergens
pathogens
pollution
tobacco smoke

Question 22

what is an acute lung attack in school age children?

Answer 22

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

Question 23

what is omalizumab?

Answer 23

humanised anti-IgE monoclonal antibody

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

Question 24

what are the requirements for omalizumab prescription?

Answer 24

severe, persistent allergic asthma in 6+ yos who need continuous or frequent treatment w oral corticosteroids
documented compliance
total serum IgE between 30-1500

Question 25

what is mepolizumab?

Answer 25

anti IL-5 antibody

regulated growth, recruitment, activation and eosinophil survival

Question 26

what are the requirements for mepolizumab?

Answer 26

blood eosinophils >300cells/mcl in last year
at least 4 exacerbations requiring oral steroids in last year
6+ years old