CVR asthma and respiratory immunology Flashcards
cardinal features of asthma (4)
- wheeze
- atopy
- reversible airflow obstruction
- airway inflammation
what do you test for to confirm asthma diagnosis? (3)
- atopy
- reversible airflow obstruction
- airway inflammation -> eosinophilia and type 2 - lymphocytes
way to check for reversible lung obstruction
lung function tests
e.g. spirometry (obtain flow volume loop from this)
what does allergic reaction cause in the airway? (2)
- airway remodelling
2. inflammation
which layers are affected in the airway during allergic asthma?
all of them
(bronchial epithelium, matrix, smooth muscle)
why do only some people who have allergies have asthma?
genetic susceptibility
what genes are more prevalent in asthma?
IL-33 gene
GSDMB
What is type 2 immunity?
the adaptive response to allergen exposure in atopic individuals`
what are the antigen-presenting cells in the lung?
dendritic cells
what do dendritic cells carry antigens via in the type 2 immune response?
MHC class II -> go to lymph nodes, causes TH0 cells to turn in to TH2 cells
what ILs are secreted by Th2 cells in the type 2 immune allergic response?
4,5, 13
what does IL-5 promote?
eosinophil recruitment and prolonged survival
what does IL-4 promote?
b cell secretion of IgE
what does IL-13 promote?
mucous secretion
what does activated IgE bind?
mast cells
what do mast cells release when they degranulate?
GFs, cytokines, chemokines
-> histamines, nicotinoids, type II mediators
diagnostic test for allergic sensitisation
- bloods for specific IgE antibodies
2. skin prick test (wheel and flare if allergic)
what can be exhaled in a breath test, when someone in asthmatic?
nitric oxide
-> elevated = supportive of diagnosis
what can FeNO have a role in aiding?
- asthma diagnosis
- predicting steroid responsiveness
- assessing adherence to inhaled corticosteroids (should be low if compliant)
NICE asthma diagnosis guidelines
clinical: history and examination, assess/confirm wheeze when acutely unwell
Spirometry: FEV1/FVC ratio: <0.7
Reversibility of airway obstruction: bronchodilator reversibility >=12%
Exhaled nitric oxide > 35ppb (kids), >40 (adults)
aim of asthma treatments (2) and example of how to manage asthma (1)
- reduce airway eosinophilic inflammation
- acute symptomatic relief
- severe asthma = steroid-sparing therapies
how to reduce airway eosinophilic inflammation
- inhaled corticosteroids
2. leukotriene receptor antagonists
how to provide acute symptomatic relief (2)
- beta-2agonists
2. anticholinergic therapies
examples of steroid-sparing therapies
- biologic targeted to IgE (anti-IgE AB)
2. Biologic targeted to airway eosinophils (anti-IL5-AB, anti-IL5receptor- AB)
how to corticosteroids reduce eosinophil count?
promoting apoptosis
what do corticosteroids do to type 2 mediators?
reduce them
what do corticosteroids do to mast cells in asthma?
reduce their number
what is the most important aspect of asthma management?
adherence to inhaled corticosteroids
facets of asthma management (3)
- optimal device technique
- clear asthma management plan
- adherence to inhaled corticosteroids
what must patients, even with mild asthma, always be prescribed?
a preventor
-> never just give as-required bronchodilators, always start with anti-inflammatory therapy
what do you do if patient doesn’t response to inhaled corticosteroids and/or LTRA?
refer to a specialist
-> same for children
how do beta-2 agonists help with asthma?
stimulate the beta-2 receptors in the airway, found on muscle: allows muscle to relax.
what change in environment can cause an asthma attack?
- suddenly cold
- allergen presence
what is reduced in patient with asthma caused by infection?
reduced anti-viral response
- IFN alpha, beta and lamda(?) reduced
name of anti-IgE AB used?
omalizumab
criteria to be given omalizumab?
severe, persistent allergic mediated asthma in patients aged >= 6 years. Require frequent or continuous treatment with oral corticosteroids
how is dose of omalizumab decided? (2)
weight and serum IgE
how is omalizumab given?
2-4 weekly s/c injection
what is mepolizumab?
anti-IL5-antibody
who is given mepolizumab?
people with severe eosinophilic asthma
- suitable for adults and kids >=6yrs
how does IL-5 work?
regulates growth, recruitment, activation and eosinophil survival
