asthma and respiratory immunology

Question 1

can you die of asthma?

Answer 1

YES asthma attack, approx 3/ day in uk

Question 2

core symptoms of asthma

Answer 2

1) wheeze (remember sounds from lecture), dry cough, dyspnoea

2) persistend symptoms AND attacks

Question 3

what are asthma attacks percipitated by

Answer 3

cold, exertion, allergen exposure

Question 4

what are the pathophysiology core asthma features

Answer 4

1) atopy: allergen sensitisation
2) reversible airway obstruction
3) inflammation with a) type 2 t helper cell recruitment and b) eosinophelia

Question 5

other than airway inflammation, what other pathophysiological procedure takes place in airways in asthma?

Answer 5

airway remodelling

Question 6

Why do only some people who are sensitized develop disease (asthma)?

Answer 6

1) GENETICS may determine is someone has just allergy or develops allergic diseaseee

2) environmental exposures: how much are u exposed to allergens, infections, pollution

Question 7

what is the name of the type of graph for genome wide associationstudies presentation

Answer 7

manhattan plot bc it looks likel manhattan skyline

Question 8

what is type 2 immunity and type 2 t helper cell

Answer 8

immunity where antigen is an allergen and t2 thelper cell (cd4) is a subtype of cd4 only for allergy

Question 9

what describe how type 2 immunity is triggered in asthma (how th2 cell is activated)

Answer 9

1) APC (dendritic cell: specific apc of lungs) binds allergen and presents it to
2) naive T cell (undifferentiated to helper or killer yet)
3) naive t cell differentiates to helper, and particularly Type 2 helper (allergic)

Question 10

what does the th2 cell release and what does it trigger?

Answer 10

IL4: B CELL - IgE production
IL5: eosinophils
IL13: MUCUS

Question 11

final step of immune pathway in inflammation in allergic asthma?

Answer 11

1) mast cell activated by igE and 2) eosinophils produce: histamines, eicosanoids, cytokines, chemokines, enzymes, growth factors

Question 12

what is one inappropriate and one appropriate measurement of allergic sesitization?

Answer 12

blood test screening for:
for specific igE antibodies to relevant allergens

TOTAL igE NOT SUFFICIENT to define atopy

Question 13

what are the tests doen for eosinophil count?

Answer 13

blood eosinophil count, sputum eosinophil count and exhaled nitric oxide

Question 14

abnormal levels of blood eosinophil and sputum and in who do they apply

Answer 14

> /=300 cells/mcL abnormal in patient with SUSPECTED or CONFIRMED asthma

> /=3%

Question 15

what units are nitric oxide levels counted in and where from?

Answer 15

fractional concentration of EXHALED nitric oxide

Question 16

what is nitric oxide a marker of? (primarily)

Answer 16

INDIRECT marker of th2-high eosinophilic airway inflammation

Question 17

what is nitric oxide also a marker of?

Answer 17

steroid responsiveness (if anything changes when they take short acting dose) and assessing adherence to inhaled corticosteroids (if theyve been taking their long term dose i think)

Question 18

why is nitric oxide present in asthmatic inflammation?

Answer 18

increased production of it from inflammed: activated epithelial cells

Question 19

normal levels NO in adults and children

Answer 19

<20-25 adult
<15-20 child

Question 20

NO levels to contribute to asthma diagnosis in adult and child

Answer 20

> /=40 adult ppb
/=35 child ppb

Question 21

when do you diagnose child / young operson with asthma

Answer 21

1) if they have symptoms: a) history and examination b) confirmed by doctor wheeze when acutely unwell

2) and one of the following :
a)obstructive spirometry (FEV1/FVC ratio <0.7 (adults), <0.8 (children) )

AND

bronchodilator reversibility positive. (reversibility>/= 12%)

or

NO >35 and positive peak flow variability

Question 22

order of objective tests

Answer 22

if they have sympotms
1) spirometry

2) BDR if spirometry shows obstruction (bronchodilator reversibility- checking if its reversible airway obstruction as it should be in asthma)

3) if diagnostic uncertainty remains after these consider FeNO

4) if uncertainty remains monitor peak flow variability for 2-4 weeks

Question 23

what do you do if child cant perform objective tests for some reason?

Answer 23

treat based on observation and clinical judgement
and try doing tests again every 6-12 months

Question 24

what are the 3 management types of asthma and in what case is each used?

Answer 24

1) every asthmatic is given this: reduce eosinophelic inflammation: inhaled corticosteroids or leukotriene receptor antagonist

2) for acute sympotmatic relief:
beta 2 agonist and anticholinergic therapies (smooth muscle relaxation)

3) severe asthma therapies:
biologics:
Anti-IgE antibody

Biologics targeted to airway eosinophils
Anti-interleukin-5 antibody
Anti-interleukin-5 receptor antibody

Question 25

through what mechanism do corticosteroids target macrophages and T lymphocytes

Answer 25

reduce cytokines

Question 26

through what mechanism do corticosteroids target dendritic cell and mast cell and eosinophils

Answer 26

decreasing numbers through apoptosis

Question 27

through what mechanism do corticosteroids target smooth muscle in aiway

Answer 27

incr b2 receptors
decr cytokines

Question 28

through what mechanism do corticosteroids target endothelial cells

Answer 28

decr leak

Question 29

through what mechanism do corticosteroids target epithelial cells

Answer 29

decr cytokines and mediators

Question 30

what are the 3 most critical elements for asthjma management to be effective

Answer 30

1) using machine right
2) adhering to treatment
3) HAVING CLEAR ASTHMA MANAGEMENT PLAN: its mandatory to have this plan written somewhere for patient

Question 31

what are the typical triggers in pathogenesis of acute lung attack in school age children

Answer 31

allergens + viruses/ bacteria: pathogens + pollution + tobaco smoke

Question 32

what is the pathogenesis of acute lung attack in school children- cellular level

Answer 32

the combination of the triggers leads to
1) reduced IFN a, beta and lamda leading to decreased antivrial responses and increased viral replication

2) increased airway inflammation by eosinophils (responsive to corticosteroids)

Question 33

what is the pathogenesis of acute lung attack in school children- the result seen clinically

Answer 33

reduced peak expiratory flow rate and

increased airway obstruction

resulting in acute wheeze

responsive to bronchodilators

Question 34

what are IgE antibody’s full name?

Answer 34

humanised anti-IgE monoclonal antibody

Question 35

what are the observed effects of IgE ab

Answer 35

1) BINDS IgE and prevents it from activating mast cells and basophils to stop allergic cascade

2) may lead to IgE production reduction

Question 36

what is an indicator that you could stop IgE ab therapy? is stopping it an upholding long term solution?

Answer 36

IgE production level drop. we dont know - no evidenc ethat it is

Question 37

name of anti IgE antibody drug

Answer 37

omalizulab

Question 38

criteria for eligibility for omalizulab? what proportion is that? what proportion repsonds

Answer 38

1) severe persistent asthma, has had to take 4 or more oral corticosteroids over last few years

2) 6 yrs old or older

3) optimised standard therapy

4) has DOCUMENTED COMPLIANCE to therapy

60% eligible
50-60 % respond

Question 39

goals of IgE levels with omalizulab, dosing and price?

Answer 39

30-1500 IU/ml (International Units/ ml)

dosing based on weight and serum ige 2-4 weeks s/c injections

Min 75mg 4 weekly = £1,665 /patient/year
Max 600mg 2 weekly = £26,640 /patient/year

Question 40

name of anti IL-5 anitbody drug

Answer 40

mepolizumab

Question 41

who is mepolizumab for?

Answer 41

severe eosinophilic asthma
adilts and children 6 and overBlood eosinophils >300 cells/mcl in the last 12 months

At least 4 exacerbations requiring oral steroids in the last 12 months

Trial for 12 months – 50% reduction in attacks, then continue

Question 42

characteristics of those who respond best to mepolizumab

Answer 42

elevated blood eosinophils
number of previous exacerbations
dose of inhaled steroids

Question 43

is mepolizumab more effective in children or adults?

Answer 43

adults, more trials need to be done specific for children

Question 44

what is dupilumab?

Answer 44

anti-IL4Ra Ab, shared receptor for IL-4 AND IL13

Question 45

WHAT is unique and very clinically important about dupilumab?

Answer 45

fewer asthma attacks AND improved lung function (has never been succeded before by other drug)

Question 46

what does IL-5 and 13 do?

Answer 46

recruit b cells

Question 47

what is the order in which you perscribe drugs for asthma in adults from suspected asthma to severe asthma

Answer 47

1) start low dose ICS and monitor
if infrequent short lived wheeze
2) regular preventer: low dose ICS
3) INITIAL ADD ON: add inhaled LABA (long acting …) - (fixed dose SMART)
4) ADDItional controlled therapies: increase ICS to medium or add LTRA
+ consider stopping LABA if not effective

5) specialist referal

Question 48

differences of treatment doses for children

Answer 48

1) low dose replaced by very low dose/ paediatric dose

2) medium dose replaced by low dose

3) children <5 cant take LABA ONLY LTRA

Question 49

SOLUTION FOR BETTER ADHERANCE TO ICS THERAPIES

Answer 49

SMART: single inhaler maintenance reliever therapy.