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BRS YR2 > Asthma and Respiratory Immunology > Flashcards

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
  • Atopy/allergen sensitisations
  • reversible airflow obstruction
  • airway inflammation (Eosinophilia and T2-Lymphocytes)
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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
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3
Q

How is a reversible airflow obstruction diagnosed?

A

lung function test (spirology)
- flow volume loop with scooped black line
(changes to normal with treatment)

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4
Q

What must be tested in the diagnosis of asthma?

A
  • evidence of inflammation, eosinophilia (biopsy)
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5
Q

What causes asthma?

A
  • suspetibility to asthma
  • exposure and sensitisation to pathogens
  • inflammation and airway remodelling (changes in the structure)
  • changes in epithelial (increased goblet cells)
  • increased matrix
  • increased sized and number of smooth muscle cells
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6
Q

Why do only some people that are sensitized develop disease?

A

need the underlying genetic susceptibly to develop it.

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7
Q

What genes have been consistently shown to cause an increased susceptibility to asthma?

A
  • IL33

- GSDMB

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8
Q

Is one gene enough to cause a susceptibility to asthma?

A

no - multifactorial cause

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9
Q

Why is type II immunity important in allergic asthma?

A
  • determines the tests done
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10
Q

What is the pathway of a antigen causing eosinophilic airway inflammation?

A
  • antigen
  • antigen presenting cell (MHC class II)
  • Th0
  • Th2
  • release of IL-4, -5, -13
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11
Q

What does IL-5 do?

A

recruitment and survival of eosinophils

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12
Q

What does IL-4 do?

A

conversion of B cells to secrete IGE

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13
Q

What does IL-13 do?

A

involved in mucus secretion

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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, and chemokines
  • causing the allergic reactions: histamines, elcosanoids
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15
Q

How do you test for allergic sensitization?

A
  • skin prink tests

- blood tests

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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
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17
Q

What tested in the blood tests for allergic sensitisation?

A
  • specific to IgE antibodies to allergens of interest

- total IgE alone is not sufficient to define atropy.

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18
Q

What tests are done for eosinophilia?

A
  • blood test (when stable)
  • induced sputum test
  • exhaled nitric oxide.
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19
Q

What blood eosinophil count (when stable) is indicative of asthma?

A

> 300 cells/mcl is abnormal

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20
Q

What induced sputum eosinophil count if abnormal?

A

> /= 2.5%

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21
Q

What is exhaled nitric oxide?

A

a non-invasive biomarker of airway (type-2) inflammstion

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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
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23
Q

When should exhaled nitric oxide not be used in the diagnosis of asthma?

A

when steroids have been use

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24
Q

What can exhaled nitric oxide also do?

A
  • prediction of steroid responsiveness

- assessing adherence to inhaled corticosteroids

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25
Q

What is needed to confirm eosinophilic inflammation?

A
  • symptoms
  • lung function test
  • blood/airways eosinophils
  • exhaled nitric oxide
26
Q

What is involved in the clinical assessment for asthma confirmation?

A
  • history and examination

- confirm the presence of a wheeze

27
Q

What are the objective tests done when looking to confirm a diagnosis of asthma?

A
  • airway obstruction on spirometry
  • reversible airway obstruction
  • exhaled nitric oxide
28
Q

What FEV1/FVC ratio would suggest asthma?

A

<0.7

29
Q

What bronchodilator reversibility would suggest asthma?

A

> /= 12%

30
Q

What exhaled nitric oxide would be indicative of asthma?

A

children: >35ppb
adults: >40ppb

31
Q

When should asthma be diagnosed in those aged 5-16?

A

symptoms of asthma and:
- FeNO level of >35 and positive peak flow variability
OR
- obstructive spirometry and positive bronchodilator reversibility

32
Q

In what order should be the tests be performed?

A 
- spirometry
if obstruction:
- BDR
if uncertainty remains:
- FeNO
if uncertainty remains:
- peak flow variability
33
Q

How is asthma managed?

A
  • reduce airway eosinophilic inflammation
  • acute symptomatic relief
  • severe asthma
34
Q

How do you reduce airway eosinophilic inflammation?

A
  • inhaled corticosteroids
    (target and reduce eosinophilic inflammation)
  • leukotriene receptor antagonists
35
Q

What is the maintenance therapy given to all patients with asthma (irrelevant of severity)?

A
  • inhaled corticosteroids
    (target and reduce eosinophilic inflammation)
  • leukotriene receptor antagonists
36
Q

What is used for acute symptomatic relief?

A
  • Beta-2 agonists
  • anticholinergic therapies
    (smooth muscle relaxation)
37
Q

Why is reducing eosinophilic inflammation necessary?

A

needed to prevent asthmatic death

38
Q

How often is acute symptomatic relief used?

A
  • as and when needed during an attack

- NOT used regularly

39
Q

What is used for those with severe asthma that are not responding to the other treatments?

A

Steroid Sparing Therapies

  • Biologic targeting IgE
  • Biologics targeted to airway eosinophils
40
Q

What are some examples of Biologics targeting airway eosinophils?

A
  • Anti-IL-5 antibody

- Anti-IL-5 receptor antibody

41
Q

Why are corticosteroids used?

A
  • reduce the number of eosinophils by promoting apoptosis
  • reduce the type 2 mediators released by the TH2 cells
  • Reduce mast cell numbers
  • some impact and prevent remodelling
42
Q

What are the most important aspects of asthma management?

A
  • optimal device and techniques
  • clear asthma management plan
  • ensure adherence to inhaled corticosteroids
43
Q

How can adherence be monitored?

A

electric adherence monitoring - attached to inhaler

44
Q

What can be prescribed if ICS are not being effective?

A

Leukotriene receptor agonists FIRST before considering escalation

45
Q

What is the pathogenesis of an acute lung attack in children?

A

Multifactorial exposure

  • reduced antiviral response
  • reduced peak expiratory flow (acute wheeze)
  • increased eosinophilic inflammation
46
Q

What happens when an infection is the primary cause of an asthma attack?

A
  • reduced IFN-alpha, IFN-beta, IFN-lambda
  • reduced antiviral responses
  • increased viral replication leading to prolonged illness
47
Q

What can cause an acute lung attack?

A

multifactorial exposure

  • background exposure to allergens
  • pollution
  • sudden exposure
48
Q

Is obstructive reduced flow reversible during an attack?

A

no

49
Q

How are acute lung attacks managed?

A

high dose systemic steroids (usually with prednisolone)

50
Q

What is anti-IgE antibody therapy?

A

humanised anti-IgE monoclonal antibody

51
Q

What does anti-IgE antibody therapy do?

A

binds and captures circulating IgE to prevent interaction with mast cells and basophils to stop and allergic cascade

52
Q

What are the impacts of long term use of anti-IgE antibody therapy?

A
  • IgE production decreases

- therefore, therapy may not be needed indefinitely

53
Q

What is the criteria for the use of Omalizumab (anti-IgE antibody therapy)?

A
  • 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
Q

How is Omalizumab administered?

A
  • based on weight and serum IgE

- 2/4 weekly subcutaneous injections

55
Q

When is Mepolizumab (Anti-IL5 antibody therapy) used?

A
  • 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
Q

What is Omalizumab?

A

anti-IgE antibody therapy

57
Q

What is Mepolizumab?

A

Anti-IL5 antibody therapy

58
Q

What does Mepolizumab do?

A

reduced regulation of growth, recruitment and survival of eosinophils

59
Q

What is the process of administering Mepolizumab?

A

Trial for 12 months

if 50% reduction in attacks, continue

60
Q

What is Dipulimab?

A

Anti-IL4RA

  • target IL4 and IL13
  • prevents IgE and mucus secretion
61
Q

What is Tezepelumab?

A

Anti-TSLP

  • prevents eosinophilia
  • upstream of all immune responses
  • could target the initiation of disease and attacks

BRS YR2 (70 decks)

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