1b Asthma and Respiratory Immunology Flashcards
What are the cardinal clinical features of asthma?
Wheeze / dry cough / Dyspnoea
What is the definition of asthma?
Reversible airflow obstruction
Which part of breathing is affected by asthma?
Expiration - above the X axis on a flow volume loop
What happens to the FEV1:FVC ratio is asthma?
reduces
What happens to the curve on a flow volume loop in a patient with asthma?
Sinks inwards - moves outwards with the use of a bronchodilator
What type of medication pattern is needed to help asthma?
regular doses of anti-inflammatory medication, with increased during an attack - useless as a one off therapy
Which immune cell is found in the airways of people with asthma?
Eosinophils
What sound will a reversible airflow obstruction make?
wheeze
What happens to the the airway wall in a patient with asthma?
Thickening of airway wall due to airway remodelling - eosinophilic inflammation, thicker matrix and thicker smooth muscle
Why do only some people who are sensitized develop disease (asthma)?
Some people have sensitization to different allergens, however then a genetic succespibility then determines whether you have asthma or not
What is seen when doing GWAS for asthma susceptibility?
Some genes are specifically associated with asthma
However not a single gene which causes – more multifactorial and polygenic
Which are the three main interleukins which are prominent in asthma
IL-4, IL-5 and IL-13
What do the interleukins produced in allergic asthma cause?
VCAM-1 expression
mast cell proliferation
IgE synthesis
Mucin secretion
What is the type of helper cell which is enlisted in allergic asthma?
Type 2 helper cell
Which IL increases mucus production?
IL-13
What does IL-4 do in allergic asthma?
finds plasma cells to secrete IgE which exacerbates the allergic reaction
What are the tests for allergic sensitization?
Blood tests – for specific IgE antibodies to allergens of interest
Total IgE alone not sufficient to define atopy
What is an important inflammatory change to look for in Asthma?
Inflammatory eosinophilia
What is an abnormal blood eosinophil count for a patient with suspected / confirmed asthma?
> or equal to 300 cells / mcl
What is the routine breath test done to test for eosinophilia?
exhale nitric oxide
What is an abnormal result for induced sputum eosinophil count?
greater than or equal to 3%
What is FeNO?
Fraction of Exhaled Nitric Oxide
How is FeNO used diagnostically?
Fractional concentration of exhaled nitric oxide (FeNO) is a quantitative, non-invasive and safe method of measuring airway inflammation and is an indirect marker of T2-high eosinophilic airway inflammation in asthma
What is FeNO used to do?
Aid asthma diagnosis
predicting steroid responsiveness
assessing adherance to inhaled corticosteroids
What are the three objective tests which should be completed in order to make a clinical diagnosis of asthma?
Airway obstruction on spirometry
Reversible airway obstruction
Exhaled nitric oxide (FeNO)
What is the normal range of REV/FVC ratio in adults and children?
FEV1/FVC ratio <0.7 (adults), <0.8 (children)
What percentage change should bronchodilators make to airway obstruction for a diagnosis of asthma to be made?
Bronchodilator reversibility >12%
What are the values of exhaled nitric oxide in adults and children which suggest asthma?
> 35ppb (children), >40ppb (adults) – in a treatment naïve patient
When do you diagnose asthma in children and young people (5-16)?
if they have symptoms suggestive of asthma and:
FeNO level of 35ppb or more and positive peak flow variabilityor
obstructive spirometry and positive bronchodilator reversibility.
What is used to reduce airway inflammation?
Inhaled corticosteroids (ICS)
Leukotriene receptor antagonists
What medications are used for acute symptomatic relief?
Beta-2 agonists (smooth muscle relaxation)
Anticholinergic therapies (smooth muscle relaxation)
What are the biologics used to target airway eosinophillia?
Anti-interleukin-5 antibody
Anti-interleukin-5 receptor antibody
Describe the airway of a patient with asthma?
Tightening, inflammation and mucus
What medication helps to reduce airway eosinophilia?
steroids
How do steroids reduce airway eosinophilia?
- reducing recruitment from the bone marrow
- inducing apoptosis in eosinophils
What is the benefit of inhaled steroids?
Taken directly to the tissue of interest
What is the most important aspect of asthma management?
Optimal edvice and technique
Clear asthma management plan
Adherence to inhaled corticosteroids
What is the pathogenesis of an acute lung attack in school age children?
Allergens + pathogens + pollution + tobacco smoke
What happens to PEF in asthma?
Reduced peak expiratory flow rate and increased airway obstruction resulting in an acute wheeze, responsive to bronchodilators
What is anti-IgE antibody therapy?
Humanised anti-IgE monoclonal antibody
Binds and captures circulating IgE – to prevent interaction with mast cells and basophils to stop allergic cascade
What happens to IgE production over time when patients are given anti-IgE Ab?
Decreases
Which medication is used for patients with severe, persistent allergic asthma?
Omalizumab
Which treatment is an Anti-IL5 antibody?
Mepolizumab
What does Mepolizumab do?
Anti-IL5 antibody for severe eosinophilic asthma
IL-5 regulates growth, recruitment, activation and eosinophil survival
Licenced for adults and children >6 years
What are the conditions which patients need to meet in order to be given Mepolizumab?
Blood eosinophils >300 cells/mcl in the last 12 months
At least 4 exacerbations requiring oral steroids in the last 12 months
Trial for 12 months – 50% reduction in attacks, then continue
Which medication only works on people who are extremely eosinophilic?
Mepolizumab
What were the effects of treatments with mepolizumab?
Clinically significant exacerbations reduced
What happens to the airways and lungs during an asthma attack?
Tightened smooth muscles
Air trapped in alveoli
wall of airways becomes thickened and inflammed
What are the two features of the type of airway inflammation which is seen in asthma?
Eosinophilia
Type 2 Lymphocytes
