Asthma

Question 1

Name the two endotypes of asthma.

Answer 1

T2-type asthma, non-T2-type asthma

Question 2

Breakdown T2-type asthma.

Answer 2

T2-type asthma is broken down into allergic asthma which can be further categorised into exercise-induced asthma. There is also late-onset eosinophilic asthma which again can be further broken down into aspirin-exacerbated respiratory disease.

Question 3

Breakdown non-T2-type asthma.

Answer 3

Non T2 type asthma can be broken down into obesity-associated asthma, smoking-related neutrophilc asthma and smooth muscle mediated paucigranulocytic asthma.
Very late onset asthma in women is a mixture of bothT2 and non T2 type asthma

Question 4

What does epithelial damage in asthma result from?

Answer 4

The separation of columnar cells from basal cells

Question 5

Where does histamine bind?

Answer 5

Histamine mediates bronchoconstriction by binding to H1 receptors on SMC, increased vascular permeability

Question 6

What’s the function of cysteinyl leukotrienes C4 and D4?

Answer 6

Increase mucus secretion and are potential spasmogens - induce bronchoconstriction

Question 7

Function of leukotrienes B4?

Answer 7

Potent chemoattractant for immune cell recruitment

Question 8

Function of prostaglandin D2?

Answer 8

Binds via GCPR contraction of bronchial SMC and increases vascular permeability

Question 9

Which cytokines do TH2 cells release during an asthma attack?

Answer 9

TH2 cells release IL-4, IL-13 and IL-5

Question 10

What happens in response to IL-5 production during an asthma attack?

Answer 10

Infiltration of eosinophils in response to IL-5 production, releases major basic protein, peroxidase which cause tissue damage and loss of epithelium

Question 11

List and discuss the 3 methods for diagnosis of asthma.

Answer 11

1. Reversibility of airway obstruction - patients should be tested on a spirometer to measure FEV1, forced vital capacity (FVC) and FEV1/FVC ratio. Testing should be repeated after inhalation of a SABA to establish reversibility of airway obstruction
2. Hyper-responsiveness (bronchial hyperreactivity) - patients inhales increasing concentrations of methacholine (choline agonists) until there is a >20% fall in the FEV1 from the saline control value
3. Airway inflammation - eosinophil count in sputum, TH2 type asthma

Question 12

What is a biomarker for Th2-type inflammation?

Answer 12

1. In response to IL-4 and IL-13 nitric oxide is produced by inducible nitric oxide synthase in the bronchial epithelium.
2. Elevated FeNO (exhaled NO) increases the likelihood of an asthma diagnosis involving Th2-type inflammation
3. Expression of periostin, an extracellular matrix protein, is induced by IL-4 and IL-13 in airway epithelial cells and lung fibroblasts

Question 13

Name the 5 categories that are used to determine treatment requirements with controller drugs.

Answer 13

1. Inhaled corticosteroids (ICSs)
2. Long-acting B2-adrenergic receptor agonists (LABA)
3. Long-acting muscarinic antagonists
4. Leukotriene receptor antagonists (LTRAs)
5. Severe disease, IgE-specific monoclonal antibody omalizumab

Question 14

Name some short acting selective B2-adrenoceptor agonists and some long acting selective B2 adrenoceptor agonists

Answer 14

Short acting - albuterol and salbutamol
Long acting - salmeterol and formoterol

Question 15

Name a bronchodilator - methylxanthine that is used in the treatment of asthma?

Answer 15

Theophylline - metabolised by CYP450 enzymes. Cant mix with macrolides.

Question 16

Name a muscarinic antagonist

Answer 16

Ipratropium or tiotropium - competitively block muscarinic M3 receptors in the airways. M3 receptors also found on goblet cells - reduce secretions of mucus and its viscosity

Question 17

Name corticosteroids

Answer 17

Prednisolone, beclometasone and budesonide

Question 18

Name anti-IL-5 antibodies

Answer 18

Mepolizumab and reslizumab are anti IL05 monoclonal antibodies. Benralizumab are anti IL5R monoclonal antibodies

Question 19

Name release inhibitors

Answer 19

Inhaled sodium cromoglicate or nedocromil - reduce hyperactivity, don’t affect bronchodilatation

Question 20

Name leukotriene antagonists

Answer 20

Montelukast and Zafirlukast - have a structure that resembkes that of the cysteinyl leukotrienes, and they compete with these substances for the CysLT1 receptor

Question 21

Name leukotriene pathway inhibitors

Answer 21

Zileuton - inhibits 5-lipoxygenase and blocks teh formation of all leukotrienes, including LTB4. Zileuton inhibits CYP1A2 and CYP3A4 - dont mix with theophylline and warfarin