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CARDIO & RESPIRATORY > 1b Asthma and Respiratory Immunology > Flashcards

1b Asthma and Respiratory Immunology Flashcards

1
Q

What are the cardinal clinical features of asthma?

A

Wheeze / dry cough / Dyspnoea

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2
Q

What is the definition of asthma?

A

Reversible airflow obstruction

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3
Q

What are the two features of the type of airway inflammation which is seen in asthma?

A

Eosinophilia
Type 2 Lymphocytes

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3
Q

Which part of breathing is affected by asthma?

A

Expiration - above the X axis on a flow volume loop

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4
Q

What happens to the FEV1:FVC ratio is asthma?

A

reduces

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5
Q

What happens to the curve on a flow volume loop in a patient with asthma?

A

Sinks inwards - moves outwards with the use of a bronchodilator

Asthma = obstructive condition, therefore sinks the curve inwards

Also obstructive therefore expiration is more affected by the condition

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6
Q

What type of medication pattern is needed to help asthma?

A

regular doses of anti-inflammatory medication, with increased during an attack - useless as a one off therapy

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7
Q

Which immune cell is found in the airways of people with asthma?

A

Eosinophils

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8
Q

What sound will a reversible airflow obstruction make?

A

wheeze

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9
Q

What happens to the the airway wall in a patient with asthma?

A

Thickening of airway wall due to airway remodelling - eosinophilic inflammation, thicker matrix and thicker smooth muscle

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10
Q

Why do only some people who are sensitized develop disease (asthma)?

A

Some people have sensitization to different allergens, however then a genetic succespibility then determines whether you have asthma or not

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11
Q

What is seen when doing GWAS for asthma susceptibility?

A

Some genes are specifically associated with asthma
However not a single gene which causes – more multifactorial and polygenic

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12
Q

Which are the three main interleukins which are prominent in asthma

A

IL-4, IL-5 and IL-13

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13
Q

What do the interleukins produced in allergic asthma cause?

A

VCAM-1 expression
mast cell proliferation
IgE synthesis
Mucin secretion

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14
Q

What is the type of helper cell which is enlisted in allergic asthma?

A

Type 2 helper cell

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15
Q

Which IL increases mucus production?

A

IL-13

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16
Q

What does IL-4 do in allergic asthma?

A

finds plasma cells to secrete IgE which exacerbates the allergic reaction

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17
Q

What are the tests for allergic sensitization?

A

Blood tests – for specific IgE antibodies to allergens of interest

Total IgE alone not sufficient to define atopy

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18
Q

What is an important inflammatory change to look for in Asthma?

A

Inflammatory eosinophilia

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19
Q

What is an abnormal blood eosinophil count for a patient with suspected / confirmed asthma?

A

> or equal to 300 cells / mcl

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20
Q

What is the routine breath test done to test for eosinophilia?

A

exhale nitric oxide

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21
Q

What is an abnormal result for induced sputum eosinophil count?

A

greater than or equal to 3%

22
Q

What is FeNO?

A

Fraction of Exhaled Nitric Oxide

23
Q

How is FeNO used diagnostically?

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

24
Q

What is FeNO used to do?

A

Aid asthma diagnosis
predicting steroid responsiveness
assessing adherance to inhaled corticosteroids

25
Q

What are the three objective tests which should be completed in order to make a clinical diagnosis of asthma?

A

Airway obstruction on spirometry

Reversible airway obstruction
Exhaled nitric oxide (FeNO)

26
Q

What is the normal range of REV/FVC ratio in adults and children?

A

FEV1/FVC ratio <0.7 (adults), <0.8 (children)

27
Q

What percentage change should bronchodilators make to airway obstruction for a diagnosis of asthma to be made?

A

Bronchodilator reversibility >12%

28
Q

What are the values of exhaled nitric oxide in adults and children which suggest asthma?

A

> 35ppb (children), >40ppb (adults) – in a treatment naïve patient

29
Q

When do you diagnose asthma in children and young people (5-16)?

A

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.

30
Q

What is used to reduce airway inflammation?

A

Inhaled corticosteroids (ICS)
Leukotriene receptor antagonists

31
Q

What medications are used for acute symptomatic relief?

A

Beta-2 agonists (smooth muscle relaxation)
Anticholinergic therapies (smooth muscle relaxation)

32
Q

What are the biologics used to target airway eosinophillia?

A

Anti-interleukin-5 antibody
Anti-interleukin-5 receptor antibody

33
Q

Describe the airway of a patient with asthma?

A

Tightening, inflammation and mucus

34
Q

What medication helps to reduce airway eosinophilia?

A

steroids

35
Q

How do steroids reduce airway eosinophilia?

A
  1. reducing recruitment from the bone marrow
  2. inducing apoptosis in eosinophils
36
Q

What is the benefit of inhaled steroids?

A

Taken directly to the tissue of interest

37
Q

What is the most important aspect of asthma management?

A

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

38
Q

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

A

Allergens + pathogens + pollution + tobacco smoke = Allergens

Reduced antiviral response and therefore increased viral replication

Eosinophils = increased airway inflammation and matrix remodelling which thickens the airway wall

39
Q

What happens to PEF in asthma?

A

Reduced peak expiratory flow rate and increased airway obstruction resulting in an acute wheeze, responsive to bronchodilators

40
Q

What is anti-IgE antibody therapy?

A

Humanised anti-IgE monoclonal antibody

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

41
Q

What happens to IgE production over time when patients are given anti-IgE Ab?

A

Decreases

42
Q

Which medication is used for patients with severe, persistent allergic asthma?

A

Omalizumab

43
Q

Which treatment is an Anti-IL5 antibody?

A

Mepolizumab

44
Q

What does Mepolizumab do?

A

Anti-IL5 antibody for severe eosinophilic asthma

IL-5 regulates growth, recruitment, activation and eosinophil survival

Licenced for adults and children >6 years

45
Q

What are the conditions which patients need to meet in order to be given Mepolizumab?

A

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

46
Q

Which medication only works on people who are extremely eosinophilic?

A

Mepolizumab

47
Q

What were the effects of treatments with mepolizumab?

A

Clinically significant exacerbations reduced

48
Q

What happens to the airways and lungs during an asthma attack?

A

Tightened smooth muscles
Air trapped in alveoli
wall of airways becomes thickened and inflammed

49
Q

Why are bronchodilators and corticsteroids used?

A

The bronchodilators are useful to help reverse the wheeze and airway obstruction eg salbutamol as it is a beta 2 agonist

The corticosteroids are used to reduce airway inflammation eg Fluticasone, Momentasone and Budenisone

50
Q

What is Opaluzimab?

A

Anti-IgE

51
Q

What is mepoluzimab?

A

Anti-IL-5

52
Q

Describe the full pathogenesis of an asthma attack?

A
  1. Allergen which the person is sensitized to causes an immune reaction, resulting in Th2 immune cells which increase the production of Il4, Il5 and Il13
  2. IL4 = IgE
    IL5 = Eospinophils
    IL13 - Mucus
  3. Results in mucus secretion, IgE synthesis, VCAM 1 expression, eoinophillic airway inflammation and bronchoconstriction
  4. This causes the airway to undergo remodelling
    - increased matrix, increased goblet cells, thicker smooth muscle and thicker airway wall
53
Q

What recognises the allergen in an asthma attacj?

A

IgE - binds to the mast cell to cause degranulation, release of cytokines, histamines and chemokines

CARDIO & RESPIRATORY (26 decks)

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