Asthma and Respiratory Immunology Flashcards
1
Q
What are the cardinal features of asthma?
A
- wheeze (on exertion, worse with colds and allergen exposures)
- (possible) dry cough and dyspnoea
- Atopy/allergen sensitisations
- reversible airflow obstruction
- airway inflammation (Eosinophilia and T2-Lymphocytes, CD4+ cells)
2
Q
What does an untreated asthma airway look like?
A
- abnormal even at baseline
- thickened wall caused by inflammation
- increase in airway smooth muscle
- reduced lumen causes turbulent airflow, leading to wheeze
3
Q
How is a reversible airflow obstruction diagnosed?
A
- lung function test (spirometry)
- flow volume loop with scooped black line (red is normal)
- changes to normal with treatment
4
Q
What must be tested in the diagnosis of asthma?
A
- evidence of inflammation, eosinophilia (biopsy)
5
Q
What causes asthma?
A
- suspetibility to asthma
- exposure and sensitisation to pathogens
- inflammation and airway remodelling (changes in the structure)
- changes in epithelium (increased goblet cells)
- increased matrix
- increased size and number of smooth muscle cells
6
Q
Why do only some people that are sensitized develop disease?
A
need the underlying genetic susceptibly to develop it.
7
Q
What genes have been consistently shown to cause an increased susceptibility to asthma?
A
- IL33
- GSDMB
8
Q
Is one gene enough to cause a susceptibility to asthma?
A
no - multifactorial cause
9
Q
Why is type II immunity important in allergic asthma?
A
determines the tests done
10
Q
What is the pathway of an antigen causing eosinophilic airway inflammation?
A
- antigen presented to antigen presenting cell (MHC class II)
- MHCII activates Th0
- Th0 differentiates into Th1 and Th2
- TH2 releases IL-4, IL-5 and IL-13
- interleukins cause eosinophilic airway inflammation
11
Q
What does IL-5 do?
A
recruitment and survival of eosinophils
12
Q
What does IL-4 do?
A
conversion of B cells to secrete IgE
13
Q
What does IL-13 do?
A
involved in mucus secretion
14
Q
What happens when a patient is sensitised to an allergen and is the exposed to allergen again?
A
- build an allergic immune response
- IgE binds to mast cells that release growth factors, cytokines, histamines and chemokines
- causing the allergic reactions
15
Q
How do you test for allergic sensitization?
A
- skin prink tests
- blood tests
16
Q
What happens in a skin prick test?
A
- intradermal injection of a positive control and compare to the allergen.
- measure the size of the swelling caused by the allergic reaction
17
Q
What tested in the blood tests for allergic sensitisation?
A
- IgE antibodies to allergens of interest
- total IgE alone is not sufficient to define atopy
18
Q
What tests are done for eosinophilia?
A
- blood test (when stable)
- induced sputum test
- exhaled nitric oxide.
19
Q
What blood eosinophil count (when stable) is indicative of asthma?
A
> 300 cells/mcl is abnormal
20
Q
What induced sputum eosinophil count is abnormal?
A
> /= 3%
21
Q
What is exhaled nitric oxide?
A
a non-invasive biomarker of airway (type-2) eosinophilic inflammation
22
Q
How is exhaled nitric oxide used to diagnosis asthma?
A
Fractional concentration of exhaled nitric oxide
- quantitative
- non-invasive
- safe
- indirect marker of T2-high eosinophilic airway inflammation in asthma
23
Q
When should exhaled nitric oxide not be used in the diagnosis of asthma?
A
when steroids have been use
24
Q
What can exhaled nitric oxide also do?
A
- prediction of steroid responsiveness
- assessing adherence to inhaled corticosteroids
25
What is needed to confirm eosinophilic inflammation?
- symptoms
- lung function test
- blood/airways eosinophils
- exhaled nitric oxide
26
What is involved in the clinical assessment for asthma confirmation?
- history and examination
- confirm the presence of a wheeze when acutely unwell
27
What are the objective tests done when looking to confirm a diagnosis of asthma?
- airway obstruction on spirometry
- reversible airway obstruction
- exhaled nitric oxide
28
What FEV1/FVC ratio would suggest asthma?
<0.7 in adults
<0.8 in children
29
What bronchodilator reversibility would suggest asthma?
>/= 12%
30
What exhaled nitric oxide would be indicative of asthma?
children: >35ppb
adults: >40ppb
31
When should asthma be diagnosed in those aged 5-16?
symptoms of asthma and:
- exhaled nitric oxide of >35 and positive peak flow variability
OR
- obstructive spirometry and positive bronchodilator reversibility
32
In what order should be the tests be performed?
```
- spirometry
if obstruction:
- BDR
if uncertainty remains:
- exhaled nitric oxide
if uncertainty remains:
- peak flow variability
```
33
How is asthma managed?
- reduce airway eosinophilic inflammation
- acute symptomatic relief
- severe asthma - steroid sparing therapies
34
How do you reduce airway eosinophilic inflammation?
- inhaled corticosteroids
(target and reduce eosinophilic inflammation)
- leukotriene receptor antagonists
35
What is the maintenance therapy given to all patients with asthma (irrelevant of severity)?
- inhaled corticosteroids
(target and reduce eosinophilic inflammation)
- leukotriene receptor antagonists
36
What is used for acute symptomatic relief?
- Beta-2 agonists
- anticholinergic therapies
(smooth muscle relaxation)
37
Why is reducing eosinophilic inflammation necessary?
needed to prevent asthmatic death
38
How often is acute symptomatic relief used?
- as and when needed during an attack
| - NOT used regularly
39
What is used for those with severe asthma that are not responding to the other treatments?
Steroid Sparing Therapies
- Biologic targeting IgE
- Biologics targeted to airway eosinophils (anti-IL5 antibody and anti-IL5 receptor antibody)
40
What are some examples of Biologics targeting airway eosinophils?
- Anti-IL-5 antibody
- Anti-IL-5 receptor antibody
41
Why are corticosteroids used?
- reduce the number of eosinophils by promoting apoptosis
- reduce the interleukins released by the TH2 cells
- Reduce mast cell numbers
- some impact and prevent remodelling
42
What are the most important aspects of asthma management?
- optimal device and techniques
- clear asthma management plan
- ensure adherence to inhaled corticosteroids
43
How can adherence be monitored?
electric adherence monitoring - attached to inhaler
44
What can be prescribed if ICS are not being effective?
Leukotriene receptor antagonist FIRST before considering escalation
45
What is the pathogenesis of an acute lung attack in children?
Multifactorial exposure
- reduced antiviral response
- reduced peak expiratory flow (acute wheeze)
- increased eosinophilic inflammation
46
What happens when an infection is the primary cause of an asthma attack?
- reduced IFN-alpha, IFN-beta, IFN-lambda
- reduced antiviral responses
- increased viral replication leading to prolonged illness
47
What can cause an acute lung attack?
multifactorial exposure
- background exposure to allergens
- pollution
- sudden exposure
48
Is obstructive reduced flow reversible during an attack?
no
49
How are acute lung attacks managed?
high dose systemic steroids (usually with prednisolone)
50
What is anti-IgE antibody therapy?
humanised anti-IgE monoclonal antibody
51
What does anti-IgE antibody therapy do?
binds and captures circulating IgE to prevent interaction with mast cells and basophils to stop and allergic cascade
52
What are the impacts of long term use of anti-IgE antibody therapy?
- IgE production decreases
- therefore, therapy may not be needed indefinitely
- No evidence yet that stopping anti-IgE Ab after some time is a long-term solution
53
What is the criteria for the use of Omalizumab (anti-IgE antibody therapy)?
- severe, persistent allergic (IgE mediated) asthma
- >/= 6 years old
- currently use continuous and frequent treatment with oral corticosteroids (4 or more over 1 year)
- optimised standard therapy
- documented compliance
54
How is Omalizumab administered?
- based on weight and serum IgE
- 2/4 weekly subcutaneous injections
- Min 75mg 4 weekly = £1,665 /patient/year
- Max 600mg 2 weekly = £26,640 /patient/year
55
When is Mepolizumab (Anti-IL5 antibody therapy) used?
- Only in severe eosinophilic asthma
- Blood eosinophils >/= 300cells/mcl (12 months)
- >/= 6 years old
- at least 4 excacerbations requiring oral steroids in the last 12 months
56
What is Omalizumab?
anti-IgE antibody therapy
57
What is Mepolizumab?
Anti-IL5 antibody therapy
58
What does Mepolizumab do?
reduced growth, recruitment and survival of eosinophils
59
What is the process of administering Mepolizumab?
Trial for 12 months
if 50% reduction in attacks, continue
60
What is Dipulimab?
Anti-IL4RA
- target IL4 and IL13
- prevents IgE and mucus secretion
61
What is Tezepelumab?
Anti-TSLP
- prevents eosinophilia
- upstream of all immune responses
- could target the initiation of disease and attacks
62
What is the epidemiology of asthma?
- 5.4 million people in the UK currently receiving treatment for asthma
- 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. £1billion annually treating asthma
63
What are the values which diagnose reversible airflow obstruction alongside the flow-volume loop?
(FEV1/FVC)
- adults = <0.7
- children = <0.8
64
What percentage pf patients are eligible omalizumab and what percentage respond to the treatment?
- Only approx. 60% of patients are eligible
- Of those, only approx. 50-60% respond
