8.7 Cystic Fibrosis: Cause, Clinical Manifestations & Treatment

Question 1

What is the most common life limiting genetic disease in Australia?

Answer 1

Cystic fibrosis

Question 2

Why are pediatric rates of cystic fibrosis the same, but adulthood rates increasing?

Answer 2

Because children with CF are living into adulthood

Question 3

Median survival duration of people with CF

Answer 3

54.3 years

Question 4

What is the mechanism of genetic transfer of cystic fibrosis?

Answer 4

Autosomal recessive

Question 5

1 in __ Australians carry the CF gene

Answer 5

1 in 25

Question 6

1 in ____ of all live births in Australia have CF

Answer 6

2500

Question 7

Cystic fibrosis pathophysiology

Answer 7

• CFTR gene defect
• Abnormal CFTR protein
• Defective Cl- transport
• Airway surface liquid depletion
• Delayed mucociliary clearance

Question 8

In what type of cells is the CFTR protein present?

Answer 8

Epithelial cells

Question 9

List some organs that can be effected by cystic fibrosis

Answer 9

• Liver (CFTR contributes to biliary secretion)
• Pancreas (pancreatic secretion volume)
• GI tract
• Sinus (Regulates fluid volume)
• Lung (Maintains fluid volume, allowing cilia to beat)
• Sweat gland (leads to salty sweat)

Question 10

Outline some benefits of Trikafta in CF management

Answer 10

• Increased FEV1
• Reduction in pulmonary exacerbations
• Normalised sweat chloride levels

Question 11

What is the most common inherited disease?

Answer 11

Cystic fibrosis

Question 12

Which population is most commonly affected by cystic fibrosis?

Answer 12

Caucasians

Question 13

What does CFTR stand for?

Answer 13

Cystic fibrosis transmembrane conductance regulator

Question 14

List the six classifications of CFTR mutations

Answer 14

Class 1: No protein
Class 2: No traffic
Class 3: No function
Class 4: Less Function
Class 5: Less protein
Class 6: Less stable

Question 15

Describe Class I cystic fibrosis mutations

Answer 15

• No CFTR protein

Question 16

Describe Class II cystic fibrosis mutations

Answer 16

• “no traffic”
• Cystic fibrosis protein does no treach cell surface due to folding error

Question 17

Describe Class III cystic fibrosis mutations

Answer 17

• No function
• Reaches cell surface, but does not function

Question 18

Describe Class IV cystic fibrosis mutations

Answer 18

• Less function
• CFTR operates, but at a lower capacity than normal

Question 19

Describe Class V cystic fibrosis mutations

Answer 19

• Less protein
• Lower overall capacity

Question 20

Describe Class VI cystic fibrosis mutations

Answer 20

• Less stable
• More prone to breaking down

Question 21

What is the most common CFTR mutation? What is it’s class, and what does this mean?

Answer 21

• F508
• No traffic
• Folding error -> protein breakdown

Question 22

List the three overarching categories of cystic fibrosis treatment strategies

Answer 22

• Symptomatic treatment
• Genetic therapies
• CFTR modulator drugs

Question 23

List some symptomatic treatments for cystic fibrosis

Answer 23

• Antibiotics
• Mucolytics
• Pancreatic enzymes
• Hypertonic saline
• Physiotherapy
• Anti-inflammatories
• High fat diet/vitamins

Question 24

How does Ivacaftor help combat the effects of the F508 CFTR mutation?

Answer 24

• Prevents protein breakdown
• Keeps protein open longer at cell surface

Question 25

How can inhaled genetic therapies help in CF? Why does this need to be repeated?

Answer 25

- Provide correct DNA and mRNA to epithelial cells, enabling expression of functional ion channels - Needs to be repeated in order to replace functional cells that die

Question 26

Which airway epithelial cells are targeted for gene therapy in cystic fibrosis treatment?

Answer 26

Basal cells

Question 27

Describe cell-based cystic fibrosis therapy

Answer 27

- Remove some cells - Correct cells genetically in lab - Add corrected basal cells back into 'niche'