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Year 2 - BRS > 5.5 - Asthma and respiratory immunology > Flashcards

5.5 - Asthma and respiratory immunology Flashcards

1
Q

What are some epidemiology facts about asthma?

A
  • 5.4 million people in the UK currently receiving asthma treatment
  • 1.1 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 £1.5 billion annually treating asthma
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2
Q

What are the cardinal features of asthma? (5)

A
  • wheeze +/- dry cough +/- dyspnoea
  • persistent symptoms + episodes (attacks) - precipitated by exertion, colds, allergen exposure
  • atopy / allergen sensitisation
  • reversible airflow obstruction
  • airway inflammation
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3
Q

What atopic triad is seen in asthma?

A

HAEfever - Hayfever, Asthma, Eczema

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4
Q

Why do asthma patients have a wheeze?

A

Narrowed airway lumen in asthmatic patients causes turbulent flow –> wheezing noise

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5
Q

What does atopy / allergen sensitisation cause?

A

Narrowing of airway - seen with local allergen challenge where you introduce an allergen down bronchoscope, red inflamed erythematous

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6
Q

What is the airway like in normal vs asthma patients?

A
  • normal airway is patent allowing laminar flow through it
  • asthma airway even when well and not on treatment = abnormal airways with inflamed (eosinophilic) and thickened walls
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7
Q

How do we look for reversible airflow obstruction in asthma?

A
  • flow volume loop obtained through spirometry
  • scooping inwards of top part of curve (expiratory breath)
  • but it can go to normal with bronchodilation (hence reversible)
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8
Q

What is the FEV1/FVC ratio for airflow obstruction in adults and children?

A
  • <0.7 - adults
  • <0.8 - children
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9
Q

What immune cells are involved in airway inflammation?

A
  • eosinophilia
  • type 2 lymphocytes (Th2 lymphocytes - CD4+ cells)
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10
Q

Describe the pathogenesis of allergic asthma.

A
  1. starts with healthy airway wall with bronchial epithelium, matrix and smooth muscle (top to bottom)
  2. an allergen is introduced which sensitises airway –> inflammation and airway remodelling
  3. recruitment of inflammatory cells into airway (most eosinophils) and structural changes in airway –> increase in goblet cells which produce mucus
  4. amount of matrix increases, as well as amount and size of smooth muscle –> thickened airway wall
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11
Q

Why are only some people who are sensitised develop asthma?

A
  • due to genetic susceptibility of asthma - polygenic and environmental
  • some people may have allergies but not asthma
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12
Q

What do GWAS for asthma susceptibility show about the genetic cause of asthma?

A

Multigene disorder and polyfactorial - some people with asthma may have increased levels of GSDMB, but not IL33 and vice versa

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13
Q

How does type 2 immunity in asthma work?

A
  • patients with asthma have exposure to inhaled allergen (antigen)
  • this allergen is presented to and binds lung dendritic cells (APC)
  • carried via MHC class II to mediastinal lymph nodes
  • naive T cells in nodes differentiate into Th2 cell which secretes IL4, IL5 and IL13
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14
Q

What does IL-4 do?

A

Helps conversion B plasma cells secrete IgE

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15
Q

What does IL-5 do?

A

Recruits eosinophils into airways and promotes their survival causing eosinophilia

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16
Q

What does IL-13 do?

A

Involved in mucus secretion

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17
Q

Once sensitised to allergen, what happens if re-exposed?

A
  • allergic immune response
  • IgE recognises circulating antigen and binds to mast cells
  • mast cells degranulate and release histamines, cytokines, chemokines, growth factors, enzymes, eicosanoids
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18
Q

How do we test for allergic sensitisation? (2)

A
  • blood tests - for specific IgE antibodies to allergens of interest (total IgE alone not sufficient to tell you about sensitisation - atopy)
  • allergy skin prick tests - wheal and flare reaction in response to allergic reaction
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19
Q

How do we test for eosinophilia?

A
  • blood eosinophil count when stable: >300cells/mcl is abnormal (present in asthma)
  • induced sputum eosinophil count: >3% eosinophils is abnormal
  • exhaled nitric oxide
20
Q

What is fraction of exhaled nitric oxide (FeNO) - eosinophilia test?

A
  • quantitative, non-invasive and safe method of measuring airway inflammation and is an indirect marker of T2-high eosinophilic airway inflammation in asthma
  • has a role in aiding asthma diagnosis, predicting steroid responsiveness and assessing adherence to inhaled corticosteroids
21
Q

Are nitric oxide levels high or low in asthma?

A

During airway inflammation, activated epithelial cells increase production of NO

22
Q

What is involved in the clinical assessment to diagnose asthma? (2)

A
  • history and examination
  • assess/confirm wheeze when acutely unwell (doctor diagnosed wheeze)
23
Q

What objective tests are done to diagnose asthma? (3)

A
  • airway obstruction on spirometry - FEV1/FVC ratio <0.7 / 0.8 if child
  • reversible airway obstruction - bronchodilator reversibility >12%
  • exhaled nitric oxide (FeNO) > 35ppb (children), >40ppb (adults) - in a treatment naive patient
24
Q

How do we confirm asthma diagnosis in children and young people (aged 5-16)?

A
  • if they have symptoms suggestive of asthma AND
  • obstructive spirometry and positive bronchodilator reversibility (do this test first) OR
  • FeNO level of >35ppb and positive peak flow variability
25
Q

What are the three areas of asthma management?

A
  • reduce airway eosinophilic inflammation
  • acute symptomatic relief
  • severe asthma - steroid sparing therapies
26
Q

How do we reduce airway eosinophilic inflammation? (3)

A
  • inhaled corticosteroids (ICS)
  • leukotriene receptor antagonists
  • (maintenance therapy all asthma patients should be on - regular preventer)
27
Q

How do we provide acute symptomatic relief of asthma? (2)

A
  • beta-2 agonists (smooth muscle relaxation)
  • anticholinergic therapies (smooth muscle relaxation)
28
Q

How do we treat severe asthma with steroid sparing therapies? (2)

A
  • biologics targeted to IgE e.g. anti-IgE antibody
  • biologics targeted to airway eosinophils e.g. anti-IL5 antibody, anti-IL5 receptor antibody
29
Q

Why do we use corticosteroids? (6)

A
  • reduce eosinophil numbers through apoptosis
  • reduce mast cell numbers
  • reduce Th2 cells, macrophages, DCs
  • reduce mucus secretion
  • reduce cytokines and mediators
  • reduce endothelial cell leakage
30
Q

What are the most important aspects of asthma management to consider before prescribing further medication? (3)

A
  • optimal device and technique
  • clear asthma management plan
  • adherence to inhaled corticosteroids
31
Q

What is the order of treatment for adult asthma patients?

A
  • regular preventer - low dose ICS
  • initial add-on therapy - add inhaled LABA
  • additional controller therapies - consider increasing ICS to medium dose or adding LTRA (stop LABA if no response to it)
  • specialist therapies - refer patient for specialist care
32
Q

What is the order of treatment for paediatric asthma patients?

A
  • regular preventer - very low dose ICS / LTRA <5y
  • initial add-on therapy - add inhaled LABA or LTRA / add LTRA <5y
  • additional controller therapies - consider increasing ICS to low dose or adding LTRA/LABA if >5y (stop LABA if no response to it)
  • specialist therapies - refer patient for specialist care
33
Q

What is the SMART approach to improve adherence to asthma therapy?

A
  • Single inhaler Maintenance And Reliever Therapy
  • uses a single combination inhaler to deliver an ICS and quick-acting LABA to patients
  • although a fixed maintenance dose may be required, SMART can also be used as needed
  • use of SMART improves some asthma outcomes while potentially reducing the total delivered dose of ICS
34
Q

Why is UK the 3rd highest country in deaths from asthma in 10-24yo and 2nd highest for 10-14?

A

When feeling well, adults do not want to take maintenance therapy and when they get a cold/sudden allergen exposure they have a sudden attack

35
Q

What is the pathogenesis of an acute asthma attack? (School-age children)

A
  • exposure to allergens e.g. house dustmites, pathogens (virus/bacteria), pollution, tobacco smoke
  • if there is an infection predominantly, asthma patients have reduced IFN and anti-viral responses = viral replication increases = prolonged illness
  • reduced peak expiratory flow rate and increased airway obstruction –> acute wheeze, responsive to bronchodilators
  • increased airway eosinophilic inflammation, responsive to corticosteroids
36
Q

How does anti-IgE antibody therapy work?

A
  • humanised anti-IgE monoclonal antibody
  • binds and captures circulating IgE - prevents its interaction with mast cells and basophils to stop allergic cascade
  • IgE production can decrease with time if given anti-IgE AB
  • reduction in serum IgE over time means therapy may not need to be used indefinitely
37
Q

What is the downside of anti-IgE antibody therapy?

A

No evidence yet that stopping anti-IgE AB after some time is a long-term solution

38
Q

Why do we use biologics?

A

They reduce exacerbations/asthma attacks which cause death

39
Q

What is Omalizumab?

A

Commonly used anti-IgE antibody given as subcutaneous injections, effective at reducing exacerbations compared to placebo

40
Q

When is Omalizumab used?

A
  • severe, persistent allergic (IgE mediated) asthma in patients >6 years who need continuous or frequent treatment with oral corticosteroids
  • have to have optimised standard therapy with good adherence with no response
  • very expensive
41
Q

What serum IgE level is Omalizumab prescribed for?

A

Total serum IgE between 30-1500 iU/ml

42
Q

What is mepolizumab?

A
  • anti-IL5 antibody for severe eosinophilic asthma
  • IL-5 regulates growth, recruitment, activation and eosinophil survival
  • licensed for adults and children >6y
43
Q

When is mepolizumab trialled?

A
  • severe eosinophilic asthma
  • blood eosinophils >300 cells/mcl in last 12 months
  • at least 4 exacerbations requiring oral steroids in last 12 months
  • trial for 12 months and continue if 50% reduction in attacks
44
Q

Does mepolizumab seem to have a greater effect in adults or children with asthma?

A

Adults - clinically significant exacerbations reduced in adults 50% vs 27% in children

45
Q

What is dupilumab?

A
  • anti-IL4Ralpha antibody
  • IL4 receptor alpha is a shared receptor for IL4 and IL13
  • fewer asthma attacks AND improved lung function

Year 2 - BRS (84 decks)

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