Asthma

Question 1

What are the three factors involved in asthma which contribute to airway narrowing and increased resistance?

Answer 1

1. Increased thickness of airway wall (Th2/eosinophilic inflammation leads to remodelling) 2. Increased mucus (more goblet cells) 3. Increased constriction of airway smooth muscle

Question 2

What two methods are used to manage asthma

Answer 2

1. Reliver/rescue medications to rapidly reverse/prevent bronchoconstriction (B2 adrenoceptor agonists) 2. Controller medications (inhaled corticosteroids) for ongoing suppression of airway inflammation

Question 3

What mediators cause contraction of ASM in asthma attack?

Answer 3

Leukotrienes and histamine from mast cells ACh

Question 4

What receptor type is responsible for ASM contraction?

Answer 4

GPCRs

Question 5

What makes an effective reliever?

Answer 5

Rapidly relieves bronchoconstriction irrespective of the causative agent.

Question 6

SABA example?

Answer 6

Salbutamol

Question 7

What are the downsides of b2-ADR agonists in relieving asthma?

Answer 7

Doesn’t suppress airway inflammation - only widens airways.

Question 8

Two LABA examples?

Answer 8

Salmeterol Formoterol

Question 9

DIfference between salmeterol and formoterol in onset of action?

Answer 9

Salmeterol is not useful as a reliever - delayed onset Formoterol can be useful - fast onset

Question 10

What drug only reverse ACh induced constriction?

Answer 10

Ipratropium bromide

Question 11

What drug only reverses leukotriene mediated constriction?

Answer 11

Montelukast.

Question 12

How do ICS work? Give an example.

Answer 12

ICS work by reducing expression of genes and proteins that drive Th2/eosinophilic inflammatory response. Example: Fluticasone

Question 13

Why are ICS given by inhalation?

Answer 13

TO lower risk of side effects: HTN, osteo, Cushingoid features

Question 14

What do ICS do, and why are they helpful?

Answer 14

• Decreased airway inflammation - More symptom free days - Reduced asthma medication use - Improved lung function

Question 15

Why is astham sub-optimally controlled in many patients prescribed ICS?

Answer 15

1. Poor adherence to ICS use
2. Incorrect inhaler technique
3. Inadequate management of co-morbidities (obesity, use of other drugs such as beta blockers)
4. Astham heterogeneity
5. Glucocorticoid resistance (rare)

Question 16

Why are combination inhalers useful, giving an example.

Answer 16

Combination inhalers combine an ICS with a LABA

Example: Budesonide (ICS) with formoterol (LABA) to create Symbicort inhaler.

COmbined inhalers are good, as they improve adherence and reduce over-reliance on SABA only bronchodilators.

Question 17

How are LT-receptor antagonists useful in managing asthma? Give an example.

Answer 17

Leukotrienes, produced by mast cells and eosinophils, cause airway narrowing through contraction of ASM, mucus secretion and leakage of blood vessels.

LTs bind to CysLT1 receptors, causing these effects.

LT-receptor antagonists blocks this.

Example: Montelukast

Question 18

How are mAbs against IgE useful? Give an example.

Answer 18

mAbs target free IgE, preventing binding and activating of mast cells.

Used to treat astham with high levels of IgE.

Example: Omalizumab, given subcutaneously.

Question 19

How are mAbs against IL-5 / IL-5 receptors useful?

Give examples.

Answer 19

Il-5 is a cytokine that promotes proliferation of eosinophils.

Anti-IL-5 antibodies are useful when asthamatic have high IL-5 levels despite use of ICS.

Examples:

Mepolizumab - targets IL-5

Benralizumab - targets IL-5 receptors on eosinophils