Cystic Fibrosis

Question 1

What is cystic fibrosis?

Answer 1

Autosomal recessive CFTR gene disorder.

Impaired or absent transport of sodium, bicarbonate and chloride leading to thick viscous secretions and increased salt content in sweat glands.

Lungs and digestive tract.

Question 2

CF Class 1

Answer 2

No functional protein

Question 3

CF Class 2

Answer 3

Trafficking defect.

Question 4

CF Class 3

Answer 4

Defective channel regulation

Question 5

CF Class 4

Answer 5

Decreased channel conductance

Question 6

CF Class 5

Answer 6

Reduced protein synthesis.

Question 7

CF Class 6

Answer 7

Reduced protein stability

Question 8

Symptomatic treatment (primary form of treatment)

Answer 8

Relieve symptoms.
Increase life expectancy.
Primarily antimicrobials (oral, IV, inhaled)
Rigorous daily oral, inhaled and airway clearance.

Question 9

Causative Treatment

Answer 9

Restore partial to full CFTR production / function.

Depends on CF class.

Gene therapy?

Question 10

Cause of Respiratory symptoms in CF?

Answer 10

Inflammation
Infection = Pseudomonas aeruginosa, S. Aureus, H. Influenzae

Question 11

Pseudomonas Aeruginosa Treatment

Answer 11

2 antibiotics of different class.
14-21 days.
IV, or inhaled.

Typically a B lactam + Aminoglycoside or colistin (Polymyxins) or fluoroquinolone

Question 12

B-Lactam Examples

Answer 12

Piperacillin
Cefepime

Question 13

Aminoglycosides Examples

Answer 13

Gentamicin

Question 14

Respiratory Therapy

Answer 14

Bronchodilators
Saline nebuliser
DNA nebuliser
[can’t mix nebulisers]

Question 15

Bronchodilator for CF?

Answer 15

B2 Adrenoceptor Agonists.
Salbutamol.

Question 16

Saline Nebuliser for CF?

Answer 16

7% Hypertonic saline.
Increases hydration of airway mucosal layer
2-4 daily.
Facilitates clearance of airway mucus.
Increased pulmonary function.
Decreased risk of pulmonary events

Question 17

DNAase Nebuliser for CF?

Answer 17

Neutrophil derived DNA molecules contribute thickening of mucosa.
DNAase cleaves.
- a-dornase (Pulmozyme)

Question 18

Causative Treatment, drug class examples

Answer 18

Potentiators - increase the open probability of CFTR channels. (class 3 or 4 mutations )

Corrects - increase the amount of functional CFTR delivered to cell surface (class 2 mutations)

Question 19

CFTR Potentiator

Answer 19

Ivacaftor.
Facilitates Cl- transport by
potentiating CFTR and
increasing the probability
of the channel opening

Question 20

Lumacaftor

Answer 20

CFTR Modulator (corrector)
Stabilises ΔF508. Increased processing and trafficking of
mature protein to cell surface