Cystic fibrosis

Question 1

Inheritance pattern

Answer 1

Autosomal recessive

Question 2

Epidemiology

Answer 2

One of most common autosomal recessive conditions affecting Caucasians: 1:2000 live births
1:25 people carry a copy of the faulty gene

Question 3

Are babies screened for CF in UK at birth?

Answer 3

Yes

Question 4

Cause

Answer 4

Mutations in CF transmembrane conductance regulator (CFTR) gene on chromosome 7.
This is a Chloride channel (Cl-) and defect leads to a combination of defective chloride secretion and increased sodium absorption across airway epithelium.
Changes in the composition of airway surface liquid predispose the lung to chronic pulmonary infections and bronchiectasis.

Question 5

Neonatal clinical features

Answer 5

Failure to thrive
Meconium ileus
Rectal prolapse

Question 6

Children and young adults respiratory clinical features

Answer 6

Cough
Wheeze
Recurrent infections
Bronchiectasis
Pneumothorax
Haemoptysis
Respiratory failure
Cor pulmonale

Question 7

Children and young adults GI clinical features

Answer 7

Pancreatic insufficiency (DM, Steatorrhoea)
Distal intestinal obstruction syndrome
Gallstones
Cirrhosis

Question 8

Children and young adults other/’non respiratory or GI’ clinical features

Answer 8

Male infertility
Osteoporosis
Arthritis
Vasculitis
Nasal polyps
Sinusitis
Hypertrophic pulmonary osteoarthropathy

Question 9

Signs

Answer 9

Cyanosis
Finger clubbing
Bilateral coarse crackles

Question 10

Diagnosis

Answer 10

Sweat test - Sodium and chloride concentrations >60mmol/L (Usually more chloride)
Genetics - screen for common CF mutations

Question 11

Screening test for exocrine pancreatic dysfunction

Answer 11

Faecal elastase

Question 12

Tests

Answer 12

Bloods
Bacteriology (cough swab and sputum culture)
Radiology
Abdominal ultrasound
Spirometry 
Biochemistry (faecal fat analysis)
Aspergillus serology/skin test

Question 13

What type of defect is CF on spirometry

Answer 13

Obstructive

Question 14

Abdominal ultrasound: what to look for in CF

Answer 14

Fatty liver
Cirrhosis
Chronic pancreatitis

Question 15

CXR of CY patient

Answer 15

Hyperinflation

Bronchiectasis

Question 16

What Blood tests would you take

Answer 16

FBC
U and Es
LFT
Clotting
Vit A, D, E levels
Annual glucose tolerance test

Question 17

Management

Answer 17

Multidisciplinary
Management of chest, GI tract
Other:
Treatment of CF related diabetes
DEXA bone scan for osteoporosis and treatment
Arthritis, sinusitis and vasculitis 
Fertility and genetic counselling

Question 18

Management of advanced lung disease

Answer 18

Oxygen
Diuretics (cor pulmonale)
Non-invasive ventilation
Lung or heart/lung transplantation (post-transplant survival is 5 years)

Question 19

Prognosis

Answer 19

Median survival around 41 years in UK

Baby born today would expect to live longer

Question 20

Chest management

Answer 20

Physiotherapy (postural drainage, airway clearance)
Antibiotics for acute infective exacerbations
Chronic Pseudomonas is an important predictor of survival
Mucolytics may be useful e.g. DNase
Bronchodilators
Annual CXR surveillance recommended

Question 21

GI management

Answer 21

Pancreatic enzyme replacement
Fat soluble vitamin replacement (ADEK)
Ursodeoxycholic acid for impaired liver function
Cirrhosis may require liver transplant

Question 22

Mutation specific therapies for CF

Answer 22

Ivacaftor and Lumacaftor target the CFTR protein.
Ivacaftor is a CFTR potentiator and increases the open probability of CFTR channels
Lumacaftor is a CFTR corrector and increases amount of cell surface-localised protein

Question 23

Microbiological diagnosis of CF

Answer 23

Sputum culture