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BRS Flashcards (Y2) > Asthma And Respiratory Immunology > Flashcards

Asthma And Respiratory Immunology Flashcards

1
Q

What are the cardinal features of asthma?

A

Wheeze (turbulent airflow due to contracted airways)+/- dry cough +/- dyspnoea
Persistent symptoms + episodes (attacks) - precipitated by exertion, colds, allergen exposure
Atopy/allergen sensitisation
Reversible airflow obstruction
Airway inflammation
- Eosinophilia
- Type 2 - lymphocytes

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2
Q

At baseline, describe the airway of a person with asthma?

A

Abnormal airway
Airway inflammation and some narrowing at baseline

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3
Q

Does asthma affect inspiration, expiration or both?

A

Expiration
Black line - patient with asthma
Red dotted line - after bronchodilator therapy (reversible airway obstruction)

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4
Q

What does this image show?

A

Airway eosinophilia

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5
Q

Can spirometry be done with children?

A

Yes, aged 5+ with computer-aided incentive devices

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6
Q

What does this image show?

A

Local allergen challenge

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7
Q

Describe the pathogenesis of allergic asthma

A

Exposure to allergen (they are sensitised to)
Inflammation - eosinophilia
Airway remodelling - changes in airway wall (epithelium, matrix and smooth muscle increased in asthma, even at baseline - thickened airway wall)

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8
Q

Are there treatments for airway remodelling in asthma?

A

No, only for eosinophilia currently

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9
Q

Does everyone who has allergy have allergic disease (asthma) and why?

A

No, genetic susceptibility may play a role
Genetic susceptibility + allergy + environmental exposure -> allergic disease (reversible airway obstruction + eosinophilia)

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10
Q

Why isn’t gene therapy used for asthma?

A

Not a single gene defect, complex, multifactorial and polygenic
IL33, GSDMB - may play a role

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11
Q

Describe the inflammatory pathway in allergic asthma

A

Antigen/allergen recognised by APC (dendritic cell in lungs)
APC takes antigen to local mediastinal lymph node where naive t-cells are differentiated into Th2 cells
Th2 cells secrete IL-4, Il-5 and IL-13

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12
Q

What does IL-13 contribute to?

A

Mucin secretion

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13
Q

What does IL-4 do?

A

Locates plasma cells and signals them to produce IgE antibodies which exacerbates the allergic cycle (mast cell proliferation etc)

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14
Q

What does IL-5 do?

A

Central to allergic asthma
Attracts eosinophils from bone marrow, into blood, into the airways
Drives inflammation

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15
Q

Is there a singular gold standard test for asthma?

A

No

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16
Q

What are some tests for allergic sensitisation?

A

Allergy skin tests (skin prick test)
Blood tests for specific IgE antibodies to allergens of interests (total IgE alone is not sufficient)

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17
Q

What are some tests for eosinophilia?

A

Blood eosinophil count (when patient is stable) - >/= 300 cells/mcl is abnormal in a patient with suspected/confirmed asthma
Induced sputum eosinophil count - >/= 3% eosinophils is abnormal
Exhale nitric oxide (routinely used)

(Together with spirometry used to make a diagnosis of asthma)

18
Q

Identify the cells on this image

A
19
Q

What is fraction of exhaled nitric oxide (FeNO)?

A

Non-invasive (indirect) biomarker of type 2 eosinophilic airway inflammation

20
Q

What role does exhaled nitric oxide play in adherence and steroid response?

A

Plays a role in asthma diagnosis, predicting steroid responsiveness and assessing adherence to inhaled corticosteroids (sensitive to steroids)

21
Q

What are the NICE 2017 asthma diagnosis clinical guidelines for clinical assessment?

A

History & examination
Assess/confirm wheeze when acutely unwell (doctor diagnosed wheeze)

22
Q

What are the objective tests required for asthma diagnosis according to the NICE 2017 guidelines?

A

Airway obstruction on spirometry - FEV1/FVC ratio </=0.7 (adults), </=0.8 (children)
Reversible airway obstruction - bronchodilator reversibility >/=12%
Exhaled nitric oxide (FeNO) >/=35ppb (children), >/=40ppb (adults) - in a treatment naive patient

23
Q

What is the first step in asthma management?

A

Reduce airway eosinophilic inflammation:
- Inhaled corticosteroids (ICS)
- Leukotriene receptor antagonists

24
Q

What is the second step in asthma management?

A

Acute symptomatic relief:
- Beta-2 agonists (smooth muscle relaxation)
- Anticholinergic therapies (smooth muscle relaxation)

25
Q

How is severe asthma managed?

A

Steroid sparing therapies:
Biologic targeted to IgE
- Anti-IgE antibody
Biologics targeted to airway eosinophils
- Anti-interleukin-5 antibody
- Anti-interleukin-5 receptor antibody

26
Q

What is the mechanism of corticosteroids?

A

Dampen eosinophilia inflammation
Reduce the recruitment of eosinophils from bone marrow to blood to airways
Steroids induce apoptosis of eosinophils in airways (reduced recruitment and survival)

27
Q

Why are inhaled corticosteroids used?

A

Go directly to the tissue - avoiding side effects of systemic steroids on the rest of body (e.g. dampening adrenal function)

28
Q

How long must corticosteroids be taken for to see benefit?

A

At least six weeks
Need to be taken long term to maintain effect of dampening inflammation

29
Q

What basic steps are important for asthma management?

A

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

30
Q

Describe treatment progression for adults with asthma

A
31
Q

Describe treatment progression for children with asthma

A
32
Q

What is the pathogenesis of acute lung attack (school age children)?

A

Exposure to sensitised allergen/pathogen/pollution/tobacco smoke
Reduced anti-viral responses (interferons) and increased viral replication result in a prolonged illness
Increased airway eosinophilic inflammation, responsive to corticosteroids (may require systemic - oral/IV)
Reduced peak expiratory flow rate and increased airway obstruction (wheeze, responsive to bronchodilators)

33
Q

What is anti-IgE antibody therapy and how does it work?

A

Humanised anti-IgE monoclonal antibody
Binds and captures circulating IgE - prevents interaction with mast cells and basophils to stop allergic cascade
IgE production can decrease with time when patients are given anti-IgE Ab

34
Q

Does anti-IgE antibody therapy need to be used indefinitely?

A

Reduction in serum IgE over time means the therapy may not need to be used indefinitely
However, no evidence yet that stopping treatment after some time is a long-term solution

35
Q

Give an example of anti-IgE antibody

A

Omalizumab

36
Q

What are the requirements for a patient to be started on Omalizumab?

A

Severe, persistent allergic (IgE mediated) asthma in patient aged 6 and above who require continuous or frequent treatment with oral corticosteroids (4 or more courses in the previous year)
Optimised standard therapy + documented compliance
Total serum IgE between 30-1500 IU/mL

37
Q

What is the dosing of Omalizumab based on?

A

Weight and serum IgE
2-4 weekly subcutaneous injections

38
Q

What is a negative of Anti-IgE antibody therapy?

A

Expensive

39
Q

Is Omalizumab given to all patients with severe asthma?

A

No, only 60% eligible due to serum IgE range and only 50-60% of these patients actually respond

40
Q

What is Mepolizumab and how does it work?

A

Anti-IL5-antibody licensed for adults and children aged 6 and above
Used for severe eosinophilic asthma
IL-5 regulates growth, recruitment, activation and eosinophil survival - prevents this

41
Q

What are the UK recommendations for mepolizumab?

A

Severe eosinophilic asthma
Blood eosinophils >/= 300 cells/mcl in the last 12 months
At least 4 attacks requiring oral steroids in last 12 months
12 month trial - 50% reduction in attacks, then continue

BRS Flashcards (Y2) (79 decks)

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