asthma

Question 1

What are the key features of asthma?

Answer 1

1. wheeze (due to bronchial constriction) +/- dry cough 2. atopy/allergen sensitisation 3. reversible airway obstruction 4. airway inflammation (eosinophilia t2 lymphocytes)

Question 2

Pathophysiology of asthma?

Answer 2

Normal airway has laminar flow but asthmatic airway has thickened walls and increased smooth muscle so narrow lumen causes turbulent flow (wheeze). In spirometry expiration scooped showing airway obstruction.

Question 3

What is spirometry and why is it hard for young children?

Answer 3

Exhalation through mouth as fast and hard as possible. Require effort and coordination so hard for young children.

Question 4

What is a local allergen challenge and what does it show in asthma?

Answer 4

Inject allergens directly into airway and see the occlusion and inflammation of the airway lumen.

Question 5

What is the pathogenesis of asthma? What structural changes happen as a response?

Answer 5

Have susceptibility to asthma + allergen sensitisation. There is inflammation causing airway remodelling. Inflammatory cells (mostly eosinophils) reqruited to airway. Structural changes include 1. increased goblet cells in epithelium secreting mucus 2. amount of matrix increases 3. amount & size of smooth muscle cells increase. So thicker wall & inflammation

Question 6

Genetic basis of asthma?

Answer 6

Genetic predisposition to asthma + exposure to allergens –> asthma

Question 7

What are some genes increasingly expressed in asthma patients?

Answer 7

IL33 and GSDMB - mutligene & polyfactorial

Question 8

What happens in asthma when exposed to allergen?

Answer 8

Allergen (Antigen) presented to APC (dendritic cells in lungs) and taken to mediastinal lymph nodes where naïve t cells differentiate into Th2 cells & secrete cytokines (IL-4,5,13)

Question 9

What does IL-5 do in asthma?

Answer 9

IL-5 recruites esoinophils and prolongs their survival

Question 10

What does IL-4 do in asthma?

Answer 10

IL-4 help b cells convert to IgE.

Question 11

What does IL-13 do in asthma?

Answer 11

Aids mucus secretion

Question 12

Once they are sensitised what happens when asthmatics are exposed to the same allergen again?

Answer 12

Allergic response. IgE binds to mast cells causing degranulation of mast cells releasing inflammatory cytokines and chemokines eg. Histamine, t2 mediators.

Question 13

What are some tests for allergic sensitization? What do you see in each case?

Answer 13

1. Skin prick test - intradermal injection of allergen + control - if allergic reaction wheel and flare - measure. 2. IgE antibodies against specific allergens (not total IgE) blood test.

Question 14

During stable disease what eosinophil count is abnormal?

Answer 14

> 300 cells/mcl

Question 15

What tests can be done for eosinophilia? What is recommended?

Answer 15

Can look in airway for eosinophil using sputum sample. Recommended exhaled nitric oxide

Question 16

What is exhaled nitric oxide and what is it used for? What is it a marker of and what can it imply?

Answer 16

Exhaled nitric oxide is non-invasive biomarker of type 2 airway inflammation. Used for diagnosis & to see if adhering to ICS - if they arent it is very high

Question 17

What tests needed for a NICE asthma diagnosis?

Answer 17

1. clinical assesment - history & examination to confirm wheeze when unwell 2. objective tests 1. airway obstruction on spirometry FEV1/FVC ratio <0.7. 2. reversible airway obstruction - bronchodilator reversiblity >12%. 3. exhaled nitric oxide FeNO >35ppb children >40ppb in adults

Question 18

How can you diagnose asthma in children/young people (age 5-16)? (2 ways)? How many tests are needed to confirm diagnosis?

Answer 18

1. symptoms of asthma, FeNO levels >35ppb & positive peak flow variability 2. obstructive spirometry & positive bronchodilator reversibility. need at least 2 tests

Question 19

What is management for asthma? What to do in severe asthma not responding to treatments?

Answer 19

1. reduce eosinophilic inflammation (inhaled corticosteroids, leukotriene receptor antagonists for T2 inflammation) 2. acute symptomatic relief ( beta-2 agonists (smooth muscle relaxation) & anticholinergics) 3. if severe not responding to treatment - biologicals (anti-IgE antibodies, anti-IL5 antibody)

Question 20

What do inhaled corticosteroids do in asthma?

Answer 20

1. reduce eosinophil numbers via apoptosis 2. reduce T2 mediators released by th2 cells 3. reduce mast cell numbers 4. help remodelling

Question 21

What are 3 things needed for good management?

Answer 21

1. optimal device and technique 2. clear plan 3. adherence to IcS

Question 22

How can you check if patients are adherent to their corticosteroids?

Answer 22

Electronic adherence monitoring on their inhaler

Question 23

What is a regular preventor in asthma? What if they don’t respond to it?

Answer 23

Anti-inflammaotry treatment (eg. ICS, leukotriene receptor antagonist) . If don’t respond specialist

Question 24

What can happen if asthmatics don’t take their maintenance therapy?

Answer 24

Acute attack can lead to death

Question 25

What is the pathogenesis of an acute lung attack?

Answer 25

Background allergen exposure + infection and other factors. If infection have reduced antiviral responses and IFN. Background airway obstruction increases - may not be completely reversible with increased eosinophilia

Question 26

How do we treat acute asthma attacks?

Answer 26

High dose steroids - eg. Prednisolone

Question 27

What does anti-IgE antibody therapy do? When is it used?

Answer 27

Used when unresponsible to IcS. Binds IgE to prevent degranulation of mast cells and mediators released. Can decrease IgE production over time

Question 28

What is omalizumab? When is it used?

Answer 28

Anti-IgE antibody used in severe persistent IgE mediated asthma in those 6 and over Who need frequent steroids (4 or more courses in previous year). Document compliance

Question 29

What is mepolizumab? What does it do? When is it used

Answer 29

Anti-IL5 antibody. For severe eosinophilic asthma. Adults & kids above 6. blood eosinophils 300 or more in last 12 months . At least 4 exacerbations requiring oral steroids in last 12 months. Trial for 12 months - 50% reduction in attacks - continue