Cystic fibrosis

Question 1

What is cystic fibrosis?

Answer 1

Inherited genetic disorder characterised by a mutated Cystic fibrosis transmembrane conductance regulator gene (CFTR)

Question 2

Cystic fibrosis is an ___________ trait

Answer 2

autosomal recessive

Question 3

How prevalent is the mutated copy of the CFTR gene?

Answer 3

1 : 25

Most common in caucasian europeans

Question 4

What is the prevalence of symptomatic CF?

Answer 4

1 : 2500

Question 5

Where is the CFTR gene located?

Answer 5

Long arm of chromosome 7

Question 6

How many phenotypic classes of cystic fibrosis are there?

Which is most common?

Answer 6

6

phe508del is the most common (87%)

Question 7

What does the cystic fibrosis gene normally do?

Answer 7

Codes for an active transport channel for chloride, found in cells lining the lungs, intestines, pancreatic ducts, sweat glands, and reproductive organs

This regulates the liquid volume/consistency on epithelial surfaces

Question 8

A mutated CFTR gene codes for channels that dont work properly

What effect does this have on the epithelial surfaces?

Answer 8

Excessive, innate inflammation with thick, sticky mucous

Question 9

What are the characteristics of each class of CFTR mutations?

Answer 9

I - No synthesis 
II - Block in processing (most common) 
III - Block in regulation 
IV - Altered conductance 
V - Reduced synthesis 

There is a 6th but fuck knows what that does

Question 10

Why does a dysfunctional CFTR channel lead to chronic infection?

Answer 10

Increased mucous and mucostasis means microorganisms are trapped and can’t be removed using mucocilliary elevator

Excessive DNA from neutrophil apoptosis

Question 11

What are the presenting features for antenatal cystic fibrosis?

Answer 11

Common presentations are CVS and echogenic bowel

Less commonly present with perforated meconium ileus

Question 12

WHat are the presenting features of neonatal CF?

Answer 12

Common presentations:

• Neonatal screening
• Meconium ileus (10%) - stool stuck in bowel

Less commonly present with:

• Gut atresia
• Obstructive jaundice
• Vitamin deficiencies

Question 13

What are the presenting features for CF in infants and young children?

Answer 13

Common:

• Recurrent chest infections
• Failure to thrive

Rare:

• Rectal collapse
• Pseudo-Bartter’s syndrome
• Anaemia, oedema, hypoproteinaemia

Question 14

How might older children and adults present with CF?

Answer 14

Common:

• Recurrent chest infections
• Nasal polyps + sinusitis
• Infertility (males)

Rare:

• Acute pancreatitis
• Liver disease
• Pseudo-Bartter’s syndrome
• Atypical mycobacteria

Question 15

Describe the process of neonatal screening for CF?

What is it’s fault?

Answer 15

Newborn blood spot day 5 (Guthrie test)

Positive result for CF referred for clinical assessment and sweat test (chloride levels)

CF gene mutation analysis

Both stages still miss a proportion of cases

Question 16

What must the sweat test and CF gene analysis show, for an ‘inconclusive diagnosis’ of CF to be made?

Answer 16

Normal sweat chloride with 2 CFTR mutations (1 mutation has unclear consequences)

Intermediate sweat chloride with 0/1 CFTR mutation(s)

Question 17

What is the antenatal screening process for someone with CF who is pregnant?

Answer 17

Pre-implantation genetic diagnosis

Chorionic villus sampling

Amniocentesis

Question 18

What are the 2 cardinal features of Cystic fibrosis?

Answer 18

Pancreatic insufficiency

Recurrent bronchopulmonary infection

Question 19

What are the signs of pancreatic insufficiency?

Answer 19

Steatorrhea / abnormal stools:

• Pale or orange
• Very offensive
• Greasy/oily

Failure to thrive:

• May thrive well on breast milk
• May have deficiencies of fat soluble vitamins

Question 20

How is pancreatic insufficiency managed?

Answer 20

Enteric coated enzyme pellets

High energy diet

Fat soluble vitamin ad mineral supplementation

Question 21

What are the signs/effects of recurrent bronchpulmonary infection?

Answer 21

Pneumonitis
Bronchiectasis
Scarring
Abscesses

Question 22

Therapeutic targets for CF often target stages in the CF lung disease cycle

How is mucous obstruction and inflammation targetted?

Answer 22

Airway clearance physiotherapy

Dornase alfa

Hypertonic saline

Question 23

How is chronic infection targetted?

Answer 23

Antibiotics

Question 24

What antibiotic is used to target the inflammation found in CF?

Answer 24

Azithromycin

Question 25

What pathogens are typically associated with CF?

Answer 25

Staph aureus and Haemophilus influenzae in early years

Pseudomonas aeruginosa later

Question 26

What microorganisms are less commonly seen in CF?

Answer 26

Burkholderia cepacia

Stenotrophomonas maltophilia

MRSA

Atypical mycobacteria (eg M abscessus)

Lung microbiome

Question 27

CF has the potential to cause problems in the GI tract and also cause Hepatopathy

What problems could it cause in the GI tract?

Answer 27

GI dysmotility:

• Meconium ileus
• Gastro-oesophageal reflux
• Distal intestinal obstruction
• Constipation / rectal prolapse

May also cause Crohn’s disease or coeliac disease

Question 28

What proportion of CF patients suffer from hepatopathy?

Answer 28

5-10%

Question 29

What is CFTR modulator treatment?

Answer 29

Basically tries to restore function of the CFTR protein or act in it’s place

Question 30

What agents are used in CFTR modulator treatment?

Answer 30

Ivacaftor & lumicaftor

Question 31

Aside from CFTR modulator treatment, what other route of therapy is being developed for CF?

Answer 31

Gene editing / therapy