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BRS2 Term 1 > Asthma and respiratory immunology > Flashcards

Asthma and respiratory immunology Flashcards

1
Q

What are the main features of asthma?

A
  • wheeze +/- dry cough on exertion, worse w/ colds and allergen exposure
  • atopy/allergen sensitisation
  • reversible airflow obstruction
  • airway inflammation: eosinophilia, type 2- lymphocytes
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2
Q

What is an airway of an untreated asthma patient like?

A

thickened airway wall caused by inflammation (eosinophilic) and an increase in airway smooth muscle–> narrowed airway lumen

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3
Q

What causes wheeze?

A

turbulent flow of air through narrowed airways

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4
Q

What occurs during airway remodelling in asthma?

A
  • recruitment of inflammatory cells (eosinophils)
  • increased goblet cells in epithelium (secrete mucus)
  • inc. amount of matrix
  • inc. size and amount of smooth muscle
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5
Q

Why do only some people who are sensitised develop asthma?

A

genetic susceptibility

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6
Q

What genes are linked to asthma?

A
  • IL33
  • GSDMB
  • RAD50
  • CDHR3
  • IL1R1
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7
Q

How does the underlying immunology (type 2 immunity) cause the manifestations of asthma?

A
  • exposed to inhaled allergen (antigen)
  • presented to APC (dendritic cells in lung)–> carry antigen via MHC class II to mediastinal lymph nodes
  • naive Th0 cells differentiate into Th2 cells–> secrete IL-4, IL-13, and IL-5
  • IL-5 recruits eosinophils into airways, promoting their survival
  • IL-4 promotes B cells to secrete an IgE
  • IL-13 involved in mucus secretion
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8
Q

How do we test for allergic sensitisation?

A
  1. skin prick test: intradermal injection of +ve control (histamine), -ve control (saline), and allergens –> wheal and flare reaction if sensitised- measure size of wheal
  2. blood test for specific IgE antibodies for allergens of interest (total IgE alone not sufficient)
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9
Q

How do we test for eosinophilia?

A
  1. blood eosinophil count when stable (>300cells/mcl is abnormal)
  2. look in airway for eosinophils (sputum eosinophil count >2.5%= abnormal)
  3. exhaled nitric oxide (if elevated= abnormal) - helpful in diagnosis and determining adherence
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10
Q

How do we manage asthma?

A
  1. reduce airway eosinophilic inflammation–> inhaled corticosteroids or leukotriene receptor antagonists
    ^v. important in background the whole time
  2. acute symptomatic relief–> beta-2 agonists (smooth muscle relaxation) or anticholinergic therapies (smooth muscle relaxation)
  3. severe asthma- steroid sparing therapies–> biologic targeted to IgE (anti-IgE antibody) or targeted to airway eosinophils (anti-IL-5 antibody, anti-IL-5 receptor antibody )
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11
Q

What are the mechanisms of action of corticosteroids?

A
  • promote apoptosis of eosinophils
  • reduce type-2 mediators released by Th2 cells
  • reduce mast cell numbers
  • impact structural cells
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12
Q

What are the most important aspects of asthma management?

A
  • optimal device and technique
  • clear asthma management plan
  • adherence to inhaled corticosteroids !!!
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13
Q

What occurs during an acute asthma attack?

A
  • background exposure to allergens e.g. house dust
  • infection–> reduced antiviral responses (interferons) in asthma
  • pollution
  • tobacco smoke
    ^all come together to result in asthma attack
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14
Q

How do we treat an acute asthma attack?

A

high dose systemic inhaled steroids- prednisolone

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15
Q

Why do we give biologics?

A

in severe asthma, reduce exacerbations/attacks, which cause mortality

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16
Q

How does anti-IgE antibody therapy work?

A
  • humanised anti-IgE monoclonal antibody
  • binds and captures circulating IgE to present its interaction w/ mast cells and basophils to stop allergic cascade
  • IgE production can decrease w/ time, but when you stop treatment, symptoms return after a few months
    ^not disease-modifying, but manages and controls symptoms
17
Q

What are the criteria for omalizumab?

A

(anti-IgE antibody)

  • severe, persistent IgE-mediated asthma
  • > =6years old
  • frequent exacerbations
  • not responding to optimised standard therapy despite good adherence
  • total serum IgE between 30-1500 (a lot of patients not eligible)
18
Q

What is mepolizumab and the criteria for use?

A
  • anti-IL-5 antibody biologic–> causes apoptosis of eosinophils
  • for severe eosinophilic asthma
  • > =6year olds
  • blood eosinophils >=300cells/mcl in last 12 months
  • at least 4 attacks in last 12 months requiring oral steroids
  • 12 month trial- continue if 50% reduction in attacks

BRS2 Term 1 (19 decks)

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