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CARDIO & RESPIRATORY phase 1b > 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 and dyspnoea
  • Atopy/allergen sensitisations
  • reversible airflow obstruction
  • airway inflammation (Eosinophilia and T2-Lymphocytes, CD4+ cells)
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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 (red is normal)
  • 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
  • gentic 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 an 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 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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17
Q

What tests are done for eosinophilia?

A
  • blood test (when stable)
  • induced sputum test
  • exhaled nitric oxide.
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18
Q

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

A

> 300 cells/mcl is abnormal

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19
Q

What induced sputum eosinophil count if abnormal?

A

> /= 3%

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20
Q

What is exhaled nitric oxide?

A

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

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21
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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22
Q

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

A

when steroids have been use

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23
Q

What can exhaled nitric oxide also do?

A
  • prediction of steroid responsiveness
  • assessing adherence to inhaled corticosteroids
24
Q

What is involved in the clinical assessment for asthma confirmation?

A
  • history and examination
  • confirm the presence of a wheeze when acutely unwell
25
Q

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

A
  • airway obstruction on spirometry - <0.7 in adults
    <0.8 in children
  • reversible airway obstruction - bronchodilator reversibility >= 12%
  • exhaled nitric oxide >35ppb in children and >40ppb in adults
26
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

27
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
28
Q

How is asthma managed?

A
  • reduce airway eosinophilic inflammation
  • acute symptomatic relief
  • severe asthma - steroid sparing therapies
29
Q

How do you reduce airway eosinophilic inflammation?

A
  • inhaled corticosteroids
    (target and reduce eosinophilic inflammation)
  • leukotriene receptor antagonists
30
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
31
Q

What is used for acute symptomatic relief?

A
  • Beta-2 agonists
  • anticholinergic therapies
    (smooth muscle relaxation)
32
Q

Why is reducing eosinophilic inflammation necessary?

A

needed to prevent asthmatic death

33
Q

How often is acute symptomatic relief used?

A
  • as and when needed during an attack

- NOT used regularly

34
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 (anti-IL5 antibody and anti-IL5 receptor antibody)
35
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
36
Q

What are the most important aspects of asthma management?

A
  • optimal device and techniques
  • clear asthma management plan
  • ensure adherence to inhaled corticosteroids
37
Q

How can adherence be monitored?

A

electric adherence monitoring - attached to inhaler

38
Q

What can be prescribed if ICS are not being effective?

A

Leukotriene receptor agonists FIRST before considering escalation

39
Q

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

A

Multifactorial exposure

  • reduced antiviral response and increased viral replication results in a prolonged illness
  • reduced peak expiratory flow (acute wheeze)
  • increased eosinophilic inflammation
40
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
41
Q

What can cause an acute lung attack?

A

allergens
pathogens
pollution
tobacco smoke

42
Q

Is obstructive reduced flow reversible during an attack?

A

no

43
Q

How are acute lung attacks managed?

A

high dose systemic steroids (usually with prednisolone)

44
Q

What is anti-IgE antibody therapy?

A

humanised anti-IgE monoclonal antibody

45
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

46
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
  • No evidence yet that stopping anti-IgE Ab after some time is a long-term solution
47
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
48
Q

How is Omalizumab administered?

A
  • 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
49
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
50
Q

What is Omalizumab?

A

anti-IgE antibody therapy

51
Q

What is Mepolizumab?

A

Anti-IL5 antibody therapy

52
Q

What does Mepolizumab do?

A

reduced regulation of growth, recruitment and survival of eosinophils

53
Q

What is the process of administering Mepolizumab?

A

Trial for 12 months

if 50% reduction in attacks, continue

54
Q

What is Dipulimab?

A

Anti-IL4RA

  • target IL4 and IL13
  • prevents IgE and mucus secretion
55
Q

What is Tezepelumab?

A

Anti-TSLP

  • prevents eosinophilia
  • upstream of all immune responses
  • could target the initiation of disease and attacks
56
Q

What is the epidemiology of asthma?

A
  • 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
57
Q

What percentage pf patients are responsive to omalizumab and what percentage respond to the treatment?

A
  • Only approx. 60% of patients are eligible
  • Of those, only approx. 50-60% respond

CARDIO & RESPIRATORY phase 1b (14 decks)

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