Asthma/Allergy

Question 1

Where are mast cell located?

Answer 1

Generally everywhere in the body however they are most concentrated at sites where there is exposure to pathogens - GIT, resp tract, skin
They are commonly found close to vessels, nerves and glands

Question 2

What is red man syndrome?

Answer 2

Non-specific mast cell degranulation due to vancomycin treatment.

Question 3

What are some stimuli for mast cell activation

Answer 3

External

• UV light/ heat
• mechanical activation
• polybasic drugs
• morphine
• vancomycin
• allergen (IgE)
• Stings

Internal

• Hypertonic saline
• Neuropeptide
• Complement

Question 4

What are the three downstream consequences of mast cell activation?

Answer 4

Degranulation
Arachidonic acid metabolite synthesis
Cytokine synthesis

Question 5

What are the factors released in mast cell granules?

Answer 5

Histamine
Chymase
Tryptase
Heparin
TNF-alpha

Question 6

What are the factors released in the intermediate stage of mast cell activation

Answer 6

Cysteinyl leukotrienes
Prostaglandin E2
(10-30mins)

Question 7

What cytokines do mast cells produce in the late phase?

Answer 7

IL-4, IL-5 and granulocyte macrophage colony stimulating factor (GM-CSF). This is dependent on T cells and eosinophils

Question 8

What effects does histamine acting on H1 receptors have?

Answer 8

Pain and itch (sensory nerve activation)
Bronchospasm (smooth muscle contraction)
Mucus production
Vasodilation 
Increased vascular leak (via endothelials retracting from each other)
CNS activation wakefulness

Question 9

What effects does histamine acting on H2 receptors have?

Answer 9

Gastric acid secretion

Positive inotropic and chronotrophic effects

Question 10

What effects do the cysteinyl leukotrienes have?

Answer 10

Vasodilation in skeletal muscle
Hypotension (important in anaphylaxis)
Decreased CO

Asthma: Increase mucus, oedema, Airway SM shortening
Hay fever: Increase mucus, oedema

Question 11

What are the names of the cysteinyl leukotrienes produced in the intermediate phase?

Answer 11

LTC4, LTA4, LTD4 and LTE4

Question 12

What receptor do the cysteinyl leukotrienes act on?

Answer 12

CysLT1 receptor

Question 13

Some mast cell cytokines are regulated by glucocorticosteroids, which are they?

Answer 13

IL-1 and TNF

Question 14

What are some endogenous inhibitors of mast cell activation?

Answer 14

PGE2, Cortisol, adrenaline

Question 15

What are some exogenous inhibitors of mast cell activation?

Answer 15

Disodium cromoglycate, nedocromil sodium - applied topically

Question 16

What is the action of disodium cromoglycate and nedocromil sodium?

Answer 16

Inhibit mast cell degranulation and eosinophil activation and C-fibre activation
Also, activates annexin-1 which is anti-inflammatory

Question 17

What is Omalizumab?

Answer 17

Murine monoclonal antibody that sterically hinders IgE from binding to FceR1.

Question 18

Do non-steroidal anti-inflammatory drugs or COX-1 inhibitors have a beneficial effect in asthma?

Answer 18

No net beneficial effect.

Prostaglandins are a mixed beneficial and negative effectss

Question 19

What role to glucocorticosteroids play in asthma?

Answer 19

They suppress mast cell reactiveness in response to allergen via regulating cytokine and leukotriene action

Question 20

Are H1 receptor antagonists useful in treating asthma?

Answer 20

NO

Question 21

When are H1 receptor antagonists used?

Answer 21

Urticaria
Hayfever
Anaphylaxis and angioedema
atopic dermatitis
bites and stings
motion sickness

Question 22

What are the three generations of H1 receptor antagonists?

Answer 22

Sedative
Non-sedative
Newer even less sedative

Question 23

In what conditions are leukotriene receptor antagonists used?

Answer 23

Hay fever and exercise/aspirin induced asthma

Question 24

What effects for leukotriene receptor antagonists have?

Answer 24

Modest bronchdilation

Question 25

Are leukotriene receptor antagonists used by themselves?

Answer 25

Nay, they are used with GCS and B2 agonists

Question 26

Define the clinical features of asthma

Answer 26

Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing

Question 27

What host factors are related to the development of asthma?

Answer 27

Genetics - atopy and airway hyperresponsiveness
Weight - increased cytokine production
Gender - more in males before puberty, more in females after puberty

Question 28

What environmental factors effect asthma development?

Answer 28

Indoor/outdoor smoke
Diet
Pollution
Occupational sensitisers
Tobacco Smoke 
Respiratory infection - rhinovirus associated with dev. and exacerbating asthma

Question 29

What causes bronchospasm in asthma?

Answer 29

Histamines and leukotrienes

Question 30

What are the short terms events in an acute asthma attack?

Answer 30

Vasodilation
Bronchospasm
Increase mucus production
Plasma fluid leak
Irritation
Cholinergic reflex
Sensory nerve activation

Question 31

What are long term effects of asthma

Answer 31

Hypertrophy and hyperplasia of airway SM
Hyperplasia of mucus secreting cells and glands
Fibrosis of subepithelium
Angiogenesis

Question 32

What drugs are used to remove mucus plugs during acute asthma episodes?

Answer 32

None! Only coughing works and preventative drugs to reduce build up.

Question 33

What is the difference between controllers and preventers?

Answer 33

Controllers (LABA) provide constant bronchodilation

Preventers reduce mast cell activation and mast cell cytokine production