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BRS Phase 1b > Asthma and Respiratory Immunology > Flashcards

Asthma and Respiratory Immunology Flashcards

1
Q

Why is Asthma important?

A
  1. 4 million people in the UK currently receiving treatment for asthma
  2. 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

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2
Q

What are the main features of Asthma?

A 
Wheeze +/- Dry cough – on exertion, worse with colds, with allergen exposure
Atopy / allergen sensitisation
Reversible airflow obstruction
Airway inflammation
Eosinophilia
Type 2 - lymphocytes
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3
Q

What happens in Asthma?

A

Thickened airway wall, thickening caused by inflammation ( majority is eosinophilia) & baseline increase in airway smooth muscle. reversible airway obstruction.

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4
Q

Why do asthmatics have a wheeze ?

A

Narrowed airway lumen causes turbulent air flow.

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5
Q

Who is spirometry not possible for?

A

very young children, as it requires forced expulsion.

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6
Q

What is the Pathophysiology of allergic asthma?

A

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

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7
Q

Why do only some people develop Asthma after sensitisation?

A

Underlying genetic susceptibility, when you have appropriate environmental exposure you develop asthmatic manifestations.

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8
Q

Which genes have been found to be increased in people with asthma?

A

IL33
GSDMB
but asthma is polyfactorial.

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9
Q

Why is Type 2 immunity important in Allergic asthma?

A

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.

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10
Q

What are the tests for Allergic sensitisation?

A

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

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11
Q

How do you test for Eosinophilia?

A

Blood eosinophil count when stable: >300 cells /mcl is abnormal

Induced sputum eosinophil count: >2.5% eosinophils is abnormal

Exhaled nitric oxide

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12
Q

How does measuring exhaled nitric aid in asthma diagnosis?

A

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

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13
Q

How does measuring exhaled nitric aid in asthma treatment adherence and steroid response?

A

FeNO has a role in aiding asthma diagnosis, predicting steroid responsiveness and assessing adherence to inhaled corticosteroids

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14
Q

What do you need to make a diagnosis?

A

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.

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15
Q

What are the main objective tests for asthma?

A

Airway obstruction on spirometry - FEV1/FVC ration <0.7
Reversible airway obstruction - Bronchodilator reversibility >12%
Exhaled nitric oxide (FeNO) >35ppb (children), >40ppb (adults)

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16
Q

How do you reduce airway inflammation?

A 
Inhaled corticosteroids (ICS)
Leukotriene receptor antagonists
17
Q

What do you give for acute symptomatic relief?

A 
Beta-2 agonists (smooth muscle relaxation)
Anticholinergic therapies (smooth muscle relaxation)
18
Q

What is used for severe asthma?

A 
Steroid sparing therapies.
Biologic targeted to IgE
Anti-IgE antibody
Biologics targeted to airway eosinophils
Anti-interleukin-5 antibody
Anti-interleukin-5 receptor antibody
19
Q

What do

A

Reduce eosinophil numbers by promoting apoptosis.
Reduce type 2 mediators released by TH2 cells.
Reduce Mast cell numbers.

20
Q

What is the most important aspect of asthma management?

A

Optimal device and technique
Clear asthma management plan
Adherence to inhaled corticosteroids

21
Q

How can you measure adherence to the inhaler?

A

Electronic Adherence monitoring

22
Q

What happens during an acute asthma attack?

A

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).

23
Q

How does Anti-IgE antibody therapy work for asthma treatment?

A

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

24
Q

What is the criteria for Omalizumab use?

A

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

25
Q

What are some difficulties of Omalizumab?

A

Total serum IgE between 30-1500

Min 75mg 4 weekly = £1,665 /patient/year
Max 600mg 2 weekly = £26,640 /patient/year

26
Q

How is Omalizumab administered?

A

Dosing based on weight and serum IgE 2-4 weekly s/c injections

27
Q

How does Mepolizumab work?

A

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

28
Q

What are the current criteria for prescribing Mepolizumab?

A

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

BRS Phase 1b (80 decks)

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