Cystic Fibrosis

Question 1

Cystic fibrosis is an __ __ affecting multiple epithelial cells.
Chromosome __ encoding __ gene functions as __ in apical (luminal) plasma membranes of epithelial cells, regulates __ and __ of exocrine secretion

Answer 1

Autosomal recessive exocrinopathy

Chromosome 7 endocing CFTR gene, anion channel
Regulates volume and composition of exocrine secretions

Question 2

Pathophysiology of cystic fibrosis

Answer 2

CFTR protein dysfunction - impaired chloride secretion and increased sodium absorption
- Dehydrated epithelial secretions, abnormally thick and viscous mucous

1. Respiratory
   - Impaired mucociliary clearance of thick mucous favours bacterial growth
   - Nasal polyps, bronchiectasis
2. Gastrointestinal
   - Pancreatic duct obstruction prevents enzyme release (exocrine insufficiency)
   –> Malabsorption, meconium ileus
   - Progressive pancreatic damage from retained enzymes
   –> CF-related DM
   - Intestinal obstruction leads to SIBO
   - Gallstones formation
3. Non-erosive arthropathy
4. Reproductive
   - Absence of vas deference, obstructive azoospermia
   –> Infertility

Question 3

Clinical presentation of patients with cystic fibrosis

Answer 3

1. Pulmonary
   - Persistent productive cough
   - SOB and wheeze
   - Recurrent sinus and lung infection
   - Nasal polyps
   - Bronchiectasis and haemoptysis
2. Gastrointestinal
   - Meconium ileus at birth
   - Failure to thrive
   - Steatorrhoea
   - Intestinal obstruction
   - Pancreatitis - exocrine insufficiency (malabsorption)
   - CF-related diabetes
   - Biliary cirrhosis, portal hypertension
3. Infertility
4. CF related arthropathy
5. Osteopenia and osteoporosis

Question 4

What are the common colonisers in cystic fibrosis?

Answer 4

1. Staphylococcus aureus
2. Pseudomonas aeruginosa
3. Haemophilus influenzae
4. Burkholderia cepacia (pseudomonas cepacia)
5. Aspergillus

Question 5

What are the diagnostic investigations for cystic fibrosis?

Answer 5

1. Sweat chloride test - abnormally high > 60 mEq/L
   (normal < 40 mEq/L)
2. Genetic testing - DF508 and F542X
3. Dried spot test (Guthrie test)
   - immunoreactive trypsin activity

Question 6

What are the causes of false positive sweat test?

Answer 6

1. Malnutrition
2. Adrenal insufficiency
3. Glycogen storage disease
4. Nephrogenic DI
5. Hypothyroidism
6. Hypoparathyroidism
7. G6PD deficiency
8. Ectodermal dysplasia

Question 7

Who should undergo screening for cystic fibrosis?

Answer 7

BTS recommends all patients < 40 years old with bronchiectasis to undergo screening for CF

Additional points to consider:
1. Current or childhood steatorrhoea
2. Persistent isolation of Staphylococcus aureus in the sputum
3. Features of malabsorption
4. Male primary infertility
5. Upper lobe bronchiectasis

Screening investigations should include:
- Sweat chloride measurement x2
- CFTR genetic mutation analysis.

Question 8

How would you manage cystic fibrosis patient?

Answer 8

1. Multidisciplinary approach

Non-Pharmacologic
2. Regular chest physiotherapy and postural drainage
3. Deep breathing exercise
4. High calorie and fat diet

Pharmacologic and Surgical
5. Vitamin supplementation
6. Pancreatic enzyme supplementation taken with meals
7. Prophylactic antibiotics
- Flucoxacillin - staph aureus
- Amoxicillin - haemophilus, streptococcus
- Ciprofloxacin
8. Ivacaftor - CFTR modulator
9. Home NIV
10. Heart and lung transplant

End stage
11. Palliative care

Question 9

What are the treatment options for chronic pseudomonas infection?

Answer 9

1. Nebulised tobramycin, polymyxin or aztreonam
2. Bactrim
3. Azithromycin prolonged 6 months course