Asthma and respiratory immunology

Question 1

what are the cardinal features of asthma?

Answer 1

wheeze, dry cough, dyspnoea. persistent symptoms and attacks precipitated by exertion, colds, allergen exposure. Atopy/allergen sensitisation, REVERSIBLE AIRFLOW OBSTRUCTION, airway inflammation

Question 2

what is the difference between a normal airway and an asthmatic airway (not during an attack)?

Answer 2

asthmatic airway always has an inflamed and thickened wall but has relaxed smooth muscles like a normal airway

Question 3

what test can be done to prove a reversible airflow obstruction?

Answer 3

spirometry

Question 4

what will show on a spirometry test of someone with a reversible airflow obstruction?

Answer 4

scooped expiratory line on flow volume loop

Question 5

outline the pathogenesis of allergic asthma

Answer 5

exposure to an allergen causes airway inflammation and remodelling, inflammatory eosinophils are recruited, the epithelium develops increased goblet cells, increased matrix, increased amount and size of smooth muscle cells

Question 6

which genes are thought to increase susceptibility to developing asthma?

Answer 6

IL33 and GSDMB

Question 7

Describe how type 2 sensitivity results in allergic asthma

Answer 7

inhaled allergen presented to APC - dendritic cells. dendritic cells carry antigen via MHC2 to the lymph nodes in the mediastinum. Naive Th cells differentiate into Th2 and cells which secrete IL4, IL5, and IL13. secretion causes eosinophil recruitment into the airways resulting in inflammation, IgE synthesis, mucus secretion.

Question 8

What tests can be conducted for allergic sensitization?

Answer 8

skin tests using histamine, saline and allergen. blood tests for IgE antibodies - total IgE alone not sufficient to define atopy

Question 9

In testing for allergic sensitization, when are blood tests for eosinophilia useful?

Answer 9

the blood eosinophil count is only useful when the patient is well

Question 10

which white blood cell is a biomarker for allergic asthma?
what ranges of the WBC are abnormal in an asthma patient?

Answer 10

eosinophils. >300cells/mcl is abnormal when stable. >3% eosinophils in an induced sputum eosinophil count is abnormal

Question 11

Fraction of exhaled nitric oxide (FeNO) is a biomarker of which type of airway inflammation?

Answer 11

type 2, aids asthma diagnosis, predicts steroid responsiveness and assessing adherence to inhaled corticosteroids

Question 12

The NICE asthma diagnosis clinical guidelines state that clinical assessment (history and examination) are no longer enough to diagnose asthma, what else has to be done?
Why was this introduced?

Answer 12

Objective tests: spirometry showing reduced FEV1:FVC ratio, exhaled nitric oxide >40ppb, bronchodilator reversibility >12%.
Was introduced to prevent misdiagnosis of asthma as many lung diseases have same presentations as asthma

Question 13

what are the three steps in the management of asthma?

Answer 13

1. reduce airway eosinophilic inflammation
2. acute symptomatic relief
3. steroid sparing therapies in those with severe asthma

Question 14

How can we reduce airway eosinophillic inflammation?

Answer 14

inhaled corticosteroids and leukotriene receptor antagonists

Question 15

How can we relieve the acute symptoms of asthma?

Answer 15

beta-2 antagonists (smooth muscle relaxation), anticholinergic therapies

Question 16

What is involved in steroid sparing therapies to treat those with severe asthma?

Answer 16

biologics targeted to IgE (anti-IgE antibody), biologics targeted to airway eosinophils (anti-IL5 antibody)

Question 17

what is the action of inhaled corticosteroids in decreasing airway inflammation?

Answer 17

reduces number of eosinophils by promoting apoptosis, reduces type 2 mediators, impacts structural cells and reduces airway remodelling

Question 18

what are the three basics of asthma management?

Answer 18

optimal device and technique, a clear asthma management plan, adherence to inhaled corticosteroids

Question 19

outline the pathogenesis of an acute asthma attack

Answer 19

background exposure to allergen with other factors e.g. viral infection or pollution. decreased IFNs result in increased viral replication and prolonged illness, increased airway eosinophilic inflammation, reduced peak expiratory flow.

Question 20

outline the mechanism behind anti-IgE antibody therapy

Answer 20

humanised anti-IgE monoclonal antibody binds and captures circulating IgE, reduction in serum IgE over time

Question 21

What is the effect of anti-IgE monoclonal antibodies binding and capturing IgE in asthma treatment?

Answer 21

prevents interaction with mast cells and basophils to stop allergic cascade

Question 22

What is an example of anti-IgE antibody medication?

Answer 22

Omalizumab

Question 23

when is Omalizumab prescribed?

Answer 23

to severe, persistent allergic asthma in patients >6yrs who need continuous or frequent treatment with oral corticosteroids. is the optimised standard therapy with documented complience

Question 24

what is an example of anti-IL5 antibody medication?

Answer 24

Mepolizumab

Question 25

When should Mepolizumab be prescribed?

Answer 25

for severe eosinophilic asthma, blood eosinophils > 300cells/mcl in last 12 months, at least 4 exacerbations requiring oral steroids in last 12 months. trial for 12 months