Asthma Flashcards
what are the cardinal features of asthma?
wheeze +/- dry cough
atopy
reversible airflow obstruction
airway inflammation - eosinophilia, type 2 lymphocytes
what is the structure of an asthmatic airway?
thickened airway wall, inflammation eosinophil infiltration increased goblet cells increased matrix hypertrophy and hyperplasia of smooth muscle
how does an asthmatic airway change during an acute attack?
smooth muscle contracts, air gets trapped in alveoli
wall becomes more inflamed
how does type 2 hypersensitivity/immunity work in asthma?
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
what is IL-4 responsible for?
promotes plasma cells to produce IgE
what is IL-5 responsible for?
eosinophil recruitment
what is IL-13 responsible for?
mucin secretion
what are the tests for allergic sensitisation?
blood test for specific IgE antibodies to allergens of interest
allergy skin tests - wheal and flare reactions
What are 3 tests for eosinophilia?
Blood eosinophil count when stable: =/> 300 cells/mcl is abnormal
Induced sputum eosinophil count: >/= 2.5% eosinophils is abnormal
Exhaled nitrous oxide
how does exhaled nitric oxide help with eosinophil count?
indirect marker of T2-high eosinophilic airway inflammation in asthma
when are exhaled nitric oxide tests used?
aiding diagnosis
predicting steroid responsiveness
assessing adherence to corticosteroids
what is required for a full asthmatic diagnosis?
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
when should you diagnose asthma in children/YA (5-16)?
symptoms of asthma AND
FeNO 35ppb+ and positive peak flow variability
OR obstructive spirometry and positive bronchodilator reversibility
what medications should all asthmatic patients be prescribed?
maintenance anti-eosinophilics - inhaled corticosteroids, leukotriene receptor antagonists
acute symptomatic relief - beta-2-agonist, anticholinergic therapies
what additional medications should patients with severe asthma be prescribed?
steroid sparing therapies- biologics against IgE (anti-IgE)
biologics targeted to airway eosinophils: anti- IL5 AB, anti-IL5 R AB
what is the mechanism of action of corticosteroids?
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
what are the most important aspects for asthma management?
optimal device and technique by patient
clear asthma management plan
adherence to inhaled corticosteroids
what are each of the step-ups for adult asthma management escalation?
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
what may trigger an acute lung attack in school age children?
allergens
pathogens
pollution
tobacco smoke
what is an acute lung attack in school age children?
decreased IFN a,b,gamma (reduced viral responses)
reduced peak expiratory flow
eosinophilic inflammation
what is omalizumab?
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
what are the requirements for omalizumab prescription?
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
what is mepolizumab?
anti IL-5 antibody
regulated growth, recruitment, activation and eosinophil survival
for children 6+ yrs
what are the requirements for mepolizumab?
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
