Asthma And Respiratory Immunology Flashcards
cardinal features of asthma?
wheeze ± dry cough ± dyspnoea
allergen sensitisation/atopy
reversible airway obstruction
eosinophilic airway inflammation
What can cause inflammation
Eosinophilia
Th2 lymphocytes (cd4 cells)
Disease progression pattern
Persistent symptoms and attacks
What can precipitate attacks
Exertion,cold,allergen exposure
Features of flow volume loop
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
Why’d doesn’t everyone exposed to the same allergen get asthma
Genetic susceptibility plays a role
- what type of immune response dominates in allergic asthma?
type 2 → Th2 cells
What do Th2 cells do
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
How to test for allergic sensitisation
Skin tests,IgE blood tests for allergens of interest
Total IgE alone not sufficient to define atopy (diagnkse(
How to test for eosinophilia
Stable blood eosinophils if 300 cells/mcl if more then it is abnormal
Exhaled nitric oxide
induced sputum eosinophil count >3%
What is the relevance of nitric oxide
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
FeNO benchmarks
- childrenless than 15-20 normal15-20 to 35 likely Th235+ significant
- adults0 to 20-25 normal20-25 to 50 likely Th250+ significant
Asthma diagnostic investigations
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)
Criteria for diagnosis ages 5-16
Symptoms and suggestive of asthma and :
FeNO 35+ and peak flow variability
obstructive spirometry and positive bronchodilator reversibility
Do spirometers first,if seems obstructive do BDR (bronchodilator reversibility test),if still inconclusive do FeNO
How is airway eosinophilic inflammation decreased
Inhaled corticosteroids
Leukotriene receptor agonist
Acute symptomatic relief
Beta 2 agonists
Anticholinergic therapies
Both smooth muscle relaxants
SABAs
Severe asthma cases
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
how do corticosteroids help?
reduce immune cell numbers and cytokines including eosinophils
less mucus, more beta-2 receptors on smooth muscle so dilates airway smooth muscle , less leak in endothelial cells
approaches to improving adherence?+ single inhaler maintenance and reliever therapy
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
significance of interferons alpha, beta, gamma?
reduced in asthma pathophysiology → susceptibility to virus → more triggers for asthma
Basically have reduced antiviral responses and increased viral replication as a result causing prolonged illness
example of an anti-IgE antibody?
omalizumab → monoclonal antibody
When is omalizumab given
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
what antibody can be used for severe eosinophilic asthma?
anti-IL5 antibody → mepolizumab
IL-5 regulates growth recruitment activation and eosinophil survival
When is mepolizumab given
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
alternative monoclonal antibody?
dupilumab → vs shared receptor for IL-4, IL-13
treatment outcomes?
fewer asthma attacks, improved lung function
what kind of airflow occurs
turbulent which causes the wheeze
pathogenesis of allergic asthma
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.
upper airway fixed obstruction
endotracheal tumour
large airway foreign body
anti IgE antibody therapy
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
Treatment for adult asthma
Initiate with low dose ICS
Regular preventer of low dose inhaled corticosteroids
Initial add on LABA to low dose ICS (fixed dose or MART)
Additional control consider increasing ICS to medium dose or add LTRA
If no response to LABA the stop LABA
Refer to specialist care if no improvement
Use short acting beta agonists as required unless using MART move up if 3 doses a week or more being used
Treatment for paediatric asthma
Very low dose ICS for LTRA if <5 years
Initial add on use very low dose ICS plus children >5 add inhaled LABA or LTRA
Children <5 LTRA
Additional control
Consider increasing ICS to low dose or children >5 add LYRA or LABA
If nk response to LABA consider stopping
Refer to specialist care
Use short acting beta agonists as required and move up if using three doses or more
