Cystic Fibrosis

Question 1

Describe genetics of Cystic fibrosis and it’s pathophysiology.

Answer 1

Most common autosomal recessive disorder in Caucasian
- 1/25 carriers
- 1 in 2000-2500 live births
- Commonest mutation 𝚫F508

Mutation in transmembrane conductance regulator protein (CFTR) on Chr 7
-normal protein= chloride moves out of cell – no mucus build up
-abnormal protein= chloride stuck in the cell- Na+ and H2O stay with chloride- mucus build up outside of cell-> mucus collects bacteria
↓ mucociliary clearance
- Mucus sticks to mucosa-> inflammation + ↑ bacterial access = ↓ bacterial killing

Question 2

Describe the 6 classes of mutations in CFTR.

Answer 2

6 classes of mutations in CFTR
-1-3 severe disease
- Pancreatic insufficient
- -> 𝚫F508 class 2= severe disease

-4-5 milder disease
- Some pancreatic function

Question 3

Desribe complications of CF

Answer 3

• Pancreatic insufficiency
• Repeated Lung infection
• Progressive Bronchiectasis
• Scarring
• Abscesses
• Type 2 DM
• Osteoporosis

Question 4

Describe the signs/symptoms as a result of pancreatic insufficiency.

Answer 4

• Pancreatic insufficiency
• Lack of pancreatic enzymes (trypsin, colistin)
• Fat Malabsorption
• Abnormal stool-steatorrhea
• Failure to thrive

Question 5

Describe causes of repeated lung infection.

Answer 5

• Repeated Lung infection
• Pseudomonas aeruginosa
• Burkholderia cepacia (genomovar III)
• Non tuberculous mycobacteria

Question 6

Describe signs/symptoms as a result of progressive bronchiectasis

Answer 6

• Progressive Bronchiectasis (signet ring sign, tramlines, mucus pug, consolidation)

Question 7

Describe signs/symptoms as a result of abscesses

Answer 7

Abscesses
 Progressive resp decline
 Chronic sputum production
* Survival related to FEV1
* Increasing SOB

Question 8

Describe signs/symptoms that arise as a result of osteoporosis.

Answer 8

• Osteoporosis
   ↓ BMD
   ↑ fracture risk
• Risk of pneumothorax
• Nail clubbing
• Male infertility (NO vas deferens)
• Meconium ileus
• Haemoptysis due to bronchial wall destruction

Question 9

Explain the options available for antenatal and post natal screening for cystic fibrosis

Answer 9

Antenatal testing (if affected parent/sibling)
- Pre-implantation genetic diagnosis
- Chorionic villus sampling
- Amniocentesis
Neonatal screening
- New-born bloodspot day 5 (Guthrie test)
- +ve-> clinical assessment & sweat test
 Sweat test- measure chloride concentration in sweat
 >60 mmol/l= abnormal

Question 10

What are the three diagnostic outcomes as a result of postnatal or antenatal screening.

Answer 10

3 diagnostic outcomes
1. CF
2. Not CF
3. CF- screen positive inconclusive diagnosis (SPID)

Question 11

Describe management of repeated respiratory infections, scarring and abscesses.

Answer 11

For progressive resp decline
- Oxygen
- Nocturnal NIV
- Lung transplant
For mucus obstruction
- Airway clearance via physio
- Mucolytics
- Bronchodilators
For lung infection
- Antibiotics (oral, IV, nebulised)
For increased inflammation
- Azithromycin
For fibrosis/scarring
- Symptom management

Question 12

Describe management of pancreatic insufficiency

Answer 12

For pancreatic insufficiency
- Replace enzymes
- High energy diet
- Fat soluble vitamin + mineral supplement

Question 13

Describe management for Type 2 DM

Answer 13

For type 2 DM
- Insulin (oral drugs not useful)
- Problem with diet compliance

Question 14

Describe management for osteoporosis

Answer 14

For osteoporosis
- Bone protection drugs
- Weight bearing exercise

Question 15

Describe management options for Haemoptysis

Answer 15

For haemoptysis
- Minor= no treatment
- Massive= preceded by gurgling in chest
 Admit, resuscitate
 Bronchial angio + embolization

Question 16

Understand the role of transplantation in CF.

Answer 16

In CF double lung transplant will prolong life but not cure.

Question 17

Describe the modulator drugs used in management of CF.

Answer 17

Modulator drugs
-KAFTRIO
-> small benefit in lung function
-> ↓ chest exacerbations
-> ↑ weight & QoL