Asthma and Respiratory Immunology Flashcards
Why is Asthma important?
- 4 million people in the UK currently receiving treatment for asthma
- 1 million children affected (approx. 3 in every class)
On average, 3 people die of an asthma attack every day in the UK
NHS spends approx. £1billion annually treating asthma
What are the main features of Asthma?
Wheeze +/- Dry cough – on exertion, worse with colds, with allergen exposure Atopy / allergen sensitisation Reversible airflow obstruction Airway inflammation Eosinophilia Type 2 - lymphocytes
What happens in Asthma?
Thickened airway wall, thickening caused by inflammation ( majority is eosinophilia) & baseline increase in airway smooth muscle. reversible airway obstruction.
Why do asthmatics have a wheeze ?
Narrowed airway lumen causes turbulent air flow.
Who is spirometry not possible for?
very young children, as it requires forced expulsion.
What is the Pathophysiology of allergic asthma?
exposure & sensitisation to pathogen/allergen causes Inflammation & remodelling. recruitment of inflammatory cells ( mostly eosinophils), structural changes involve changes in epithelium, more goblet cells, matrix increases, amount + size of smooth muscle cells increase
Why do only some people develop Asthma after sensitisation?
Underlying genetic susceptibility, when you have appropriate environmental exposure you develop asthmatic manifestations.
Which genes have been found to be increased in people with asthma?
IL33
GSDMB
but asthma is polyfactorial.
Why is Type 2 immunity important in Allergic asthma?
Antigen presented to antigen presenting cells (dendritic cell) via MHC 2, carry to lymph nodes where T cells differentiate into T helper cell, secreting ctyokines IL-4,5,13. IL-5 recruits eosinophils into airways. IL-4 helps conversion of Bcells to secrete IgE. IL-13 involved in mucus secretion.
Re-sensitisation will cause an allergic immune response.
What are the tests for Allergic sensitisation?
Skin prick test - measure size of wheel.
Blood tests – for specific IgE antibodies to allergens of interest
Total IgE alone not sufficient to define atopy
How do you test for Eosinophilia?
Blood eosinophil count when stable: >300 cells /mcl is abnormal
Induced sputum eosinophil count: >2.5% eosinophils is abnormal
Exhaled nitric oxide
How does measuring exhaled nitric aid in asthma diagnosis?
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
How does measuring exhaled nitric aid in asthma treatment adherence and steroid response?
FeNO has a role in aiding asthma diagnosis, predicting steroid responsiveness and assessing adherence to inhaled corticosteroids
What do you need to make a diagnosis?
Diagnose asthma in children and young people (aged 5to16) 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 are the main objective tests for asthma?
Airway obstruction on spirometry - FEV1/FVC ration <0.7
Reversible airway obstruction - Bronchodilator reversibility >12%
Exhaled nitric oxide (FeNO) >35ppb (children), >40ppb (adults)
How do you reduce airway inflammation?
Inhaled corticosteroids (ICS) Leukotriene receptor antagonists
What do you give for acute symptomatic relief?
Beta-2 agonists (smooth muscle relaxation) Anticholinergic therapies (smooth muscle relaxation)
What is used for severe asthma?
Steroid sparing therapies. Biologic targeted to IgE Anti-IgE antibody Biologics targeted to airway eosinophils Anti-interleukin-5 antibody Anti-interleukin-5 receptor antibody
What do
Reduce eosinophil numbers by promoting apoptosis.
Reduce type 2 mediators released by TH2 cells.
Reduce Mast cell numbers.
What is the most important aspect of asthma management?
Optimal device and technique
Clear asthma management plan
Adherence to inhaled corticosteroids
How can you measure adherence to the inhaler?
Electronic Adherence monitoring
What happens during an acute asthma attack?
Multiple exposures to allergenic factors. e.g in infection you have reduced anti-viral response.
Background airway obstruction significantly worse, acute wheeze responsive to bronchodilators.
Increased airway eosonophilic inflammation, responsive to corticosteroids (prednisolone).
How does Anti-IgE antibody therapy work for asthma treatment?
Humanised anti-IgE monoclonal antibody
Binds and captures circulating IgE – to prevent interaction with mast cells and basophils to stop allergic cascade
IgE production can decrease with time when patients given anti-IgE Ab
Reduction in serum IgE over time means the therapy may not need to be used indefinitely
No evidence yet that stopping anti-IgE Ab after some time is a long-term solution.
e.g. Omalizumab
What is the criteria for Omalizumab use?
Severe, persistent allergic (IgE mediated) asthma in patients >6 years who need continuous or frequent treatment with oral corticosteroids
4 or more courses in the previous year
Optimised standard therapy
Documented compliance
What are some difficulties of Omalizumab?
Total serum IgE between 30-1500
Min 75mg 4 weekly = £1,665 /patient/year
Max 600mg 2 weekly = £26,640 /patient/year
How is Omalizumab administered?
Dosing based on weight and serum IgE 2-4 weekly s/c injections
How does Mepolizumab work?
Antibody to IL-5, which is important in eosinophil recruitment + survival. 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 current criteria for prescribing Mepolizumab?
Severe eosinophilic asthma
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
