Cardio - Asthma + Resp Immunology Flashcards

1
Q

What is the epidemiology of asthma in the UK?

A

→ 5.4 mil suffer from it
→ 1.1 mil are children
→ 3 per day die of asthma attack

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2
Q

What are the cardinal features of asthma?

A

→ Wheeze
→ Dry cough ( on exertion, worse w colds and allergen exposure)
→ Atopy / Allergen Sensitisation
→ Reversible airflow obstruction
→ Airway inflammation (with eosinophilia or lymphocytic Type2)

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3
Q

What are the airways like in someone with asthma?

A

→ In asthmatic airways:
→ Thickened walls due to eosinophilic inflammation
→ Relaxed smooth muscle

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4
Q

What happens to the airways during an asthma attack?

A

→ Tightened smooth muscle
→ Walls further thickened and inflamed
→ Air trapped in alveoli

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5
Q

How is reversible airflow obstruction proven?

A

→ BDR test (bronchodilator reversibility test)
→ administer bronchodilator and check
→ Change is seen between the flow volume loop before + after

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6
Q

What is the pathogenesis of allergic asthma?

A

→ allergens (e.g. pollen, dust mites, mold) irritate the bronchial epithelium
→ inflammation occurs + airway remodelling starts

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7
Q

What does airway remodelling in asthma consist of?

A

→ higher recruitment of inflammatory cells (especially eosinophils)
→ increase in goblet cells for increased mucus production
→ increase in matrix + amount and size of smooth airway muscle
→ creates a thicker airway wall

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8
Q

Why do only some people who are sensitised to allergens develop asthma?

A

→ genetic susceptibility to allergies and allergic diseases

→ environmental exposures except for allergens (e.g. infection, pollution)

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9
Q

What have GWA studies for asthma shown?

A

→ polygenic causes (ILL33, GSDMB)
→ multi-factorial regardless of genetics
→ gene therapy is not really a cure but can help with novel therapies

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10
Q

What are the cascade of reactions in Type 2 immunity is asthma?

A
→ allergen / antigen triggers dendritic cells int he lungs to become APCs with MHC class II
→ these recruit Th0 cells that differentiate into Th1 and Th2
→ Th2 cells release IL-4, IL-5, IL-13
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11
Q

What are the different interleukins responsible for in the Type 2 immune response?

A

→ IL-4 helps convert plasma cells (B-cells) + encourages production of IgE
→ IL-5 recruits eosinophils + promotes their survival
→ IL-13 involved in mucus secretion

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12
Q

How do clinics test for asthma allergy sensitisation?

A

→ allergy skin tests (wheel + flare)
→ blood tests for specific IgE antibodies to allergens of interest
→ total IgE alone however is not sufficient to define atopy

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13
Q

How do asthma clinics test for eosinophilia?

A

→ blood eosinophil count ( >300 cells/mcl is abnormal)
→ induced sputum eosinophil count ( >2.5% eosinophils is abnormal)
→ exhaled nitric oxide breath test

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14
Q

How is exhaled nitric oxide used for diagnosis of asthma?

A

→ fractional conc. of exhaled FeNO is quantitative + non-invasive
→ measures airway inflammation
→ indirect marker of T2-high eosinophilic airway inflammation in asthma

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15
Q

How is exhaled nitric oxide used to test for adherence to medication for asthmatic patients?

A

conc. of exhaled FeNO should decrease if patient is adhering to steroids (very sensitive to steroids)

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16
Q

What are the disadvantages of FeNO?

A

a single non-invasive biomarker does not reflect airway eosinophilic inflammation

17
Q

What clinical assessments need to be done for asthma according to the NICE guidelines?

A

→ history + examination

→ assess/ confirm wheeze when acutely unwell

18
Q

What are the order of diagnostic tests that need to be done for asthma according to the NICE guidelines?

A

→ airway obstruction through spirometry
→ BDR test is spirometry shows obstruction
→ if diagnostics are still uncertain, do FeNO
→ if diagnostics are still uncertain, do peak flow variability

19
Q

How are children tested for asthma if they’re unable to perform objective tests?

A

→ treat based on observation + clinical judgement

→ try doing tests agains every 6 months

20
Q

What test results are needed for a diagnosis of asthma objectively?

A

→ airway obstruction on spirometry (FEV1/FVC ratio < 0.7)
→ reversible airway obstruction - (BDR > 12%)
→ exhaled nitric oxide > 35 ppb in children or 40 ppb in adults

21
Q

What test results are needed for a diagnosis of asthma objectively in children and young people (5-16 yrs)?

A

→ FeNO level of 35 ppb or more + positive peak flow variability OR
→ obstructive spirometry + positive BDR

22
Q

What are the 3 main aspects of asthma management?

A

→ reduce airway eosinophilic inflammation
→ acute symptomatic relief
→ severe asthma prevention

23
Q

How is airway eosinophilic inflammation reduced?

A

→ inhaled corticosteroids (ICS)

→ leukotriene receptor agonists

24
Q

How is acute symptomatic relief given to asthmatic patients?

A

→ beta-2-agonists (smooth muscle relaxation)

→ anticholinergic therapies (smooth muscle relaxation)

25
Q

What are some steroid sparing therapies? (Biological)

A

→ Anti-IgE antibodies (biological targeting of IgE)

→ Anti-IL-5 antibodies or Anti-IL-5 receptor antibodies (biological targeting of airway eosinophils)

26
Q

What is the mechanism of action of corticosteroids on inflammatory cells?

A

→ reduces no. of eosinophils through apoptosis
→ reduces T-lymphocyte cytokine production
→ reduces no. of mast cells
→ reduces macrophage cytokine production
→ reduces no. of dendritic cells

27
Q

What is the mechanism of action of corticosteroids on structural cells?

A

→ reduces no. of cytokines + mediators produced by epithelial cells
→ reduces leakage from endothelial cells
→ increases beta-2 receptors but reduces cytokines from airway smooth muscle
→ reduces mucus secretion from mucus glands

28
Q

What is the most important factor in asthma management?

A

adherence to inhaled corticosteroids

29
Q

What is the regular starting treatment for asthma?

A

low dose ICS (inhaled corticosteroid)

30
Q

What is the initial add-on therapy for asthma?

A

addition of LABA to low-dose ICS (fixed dose or MART)

31
Q

What are additional controller therapies?

A

→ increasing ICS to medium dose OR
→ adding LTRA

→ if no response to LABA, scrap it

32
Q

When are biological therapies offered to asthmatic patients?

A

→ when they don’t respond to baseline steroids

→ when they have severe asthma

33
Q

What is the pathogenesis of an acute lung attack?

A

→ reduced anti-viral responses (due to infection) + increased viral replication = prolonged illness
→ reduced peak expiratory flow rate + increased airway obstruction resulting in acute wheeze, responsive to bronchodilators
→ increased airway eosinophilic inflammation, responsive corticosteroids

34
Q

What can trigger an asthma attack?

A
accumulation of:
→ allergens
→ pathogens (viral/bacterial)
→ pollution
→ tobacco smoke
35
Q

What is anti-IgE antibody therapy?

A

→ humanised anti-IgE MAB
→ binds + captures circulating IgE
→ prevents interaction with mast cells + basophils to stop allergic cascade
→ IgE production decreases over time

36
Q

What is the anti-IgE antibody therapy commonly prescribed in the UK?

A

omalizumab

37
Q

What is the criteria for anti-IgE antibody therapy?

A
→ severe, persistant allergic IgE mediated asthma in patients >6 years who need continuous or frequent treatment w oral corticosteroids
→ optimised standard therapy
→ documented compliance
→ total serum IgE between 30-1500
→ dosing based on weight and serum IgE
38
Q

What are the advantages + disadvantages to anti-IgE antibody therapies?

A

→ definite reduction in exacerbations
→ very expensive
→ many people don’t fit into the criteria for it

39
Q

When is anti-IL5-antibody therapy prescribed?

A

→ for severe eosinophilic asthma
→ licensed for adults + children over 6
→ blood eosinophils > 300 cells/mcl in the last 12 months
→ a least 4 exacerbations requiring oral steroids in the last 12 months