Cystic Fibrosis

Question 1

What is the result of CFTR abnormality?

Answer 1

Cystic fibrosis

Reduced mucociliary clearance
Increased bacterial adherence
Decreased endocytosis of bacteria

All in all leads to bacterial colonisation

• persistent inflammation
• airway ulceration and damage
• bronchiectasis

Question 2

What are common pathogens in CF?

Answer 2

Pseudomonas aeruginosa (61%)
Staph aureus (42%)
H flu (15%)
Stenotrophomonas maltophilia
Burkholderia cepacia

Question 3

What does CFTR do?

Answer 3

Usually plays a role in endocytosis and destruction

Regulates liquid volume on epithelial surface
- CF results in cilia collapse and excessive inflammation

Question 4

What happens in pseudomonas colonisation?

Answer 4

Once colonised, pseudomonas undergoes mucoid change
Forms a biofilm, microcolonies in an alginate film
Protected from host defenses
Rapidly acquires multiple antibiotic resistance

Colonisation associated with reduced life expectancy (28 vs 39 years)
Rapid decline in lung function

Question 5

What are the treatments upon discovery of pseudomonas colonisation in CF?

Answer 5

Attempt eradication with oral ciprofloxacin and nebulised colomycin for 3 months

If fails, try IV ceftazidime, and nebulised colomycin

Question 6

How do you manage recurrent respiratory tract infections in CF?

Answer 6

Treat early and aggressively with antibiotics
Oral antibiotics for staph, h flu, pneumococcus
IV for pseudomonas, stenotrophomonas, burkholderia

Use two antibiotics - Beta-lactam and aminoglycoside
If multiply-resistant, test for synergy between antibiotic combinations
Use large doses and a 2 week course

Question 7

New CF treatment?

Answer 7

Ivacaftor

First of new class of drug addressing the primary defect in CF
Is a CFTR potentiator, binding and improving Cl- transport.

Only effective in G551D patients only, which are 5-10% of patients.

Improves lung function 10%
Weight gain
Reduces sweat chloride
Improves general QOL
Expensive (£180k/year)

Question 8

When would you consider a lung transplant in CF?

Answer 8

Rapidly deteriorating lung function
FEV1 <30% predicted
Life threatening exacerbations
Estimated survival <2 years

30-40% die on waiting list

5YS 70-80%
10YS 50%
Gradual attrition due to bronchiolitis obliterans
Viewed as a measure to prolong survival and improve QOL

Question 9

What is the gene prevalence of CF?

Answer 9

1:25

Autosomal recessive

Question 10

Where is the CF gene located? How many mutations are known?

Answer 10

Long arm of Chromosome 7

1800 known mutations, of which ~30 are CF associated

Question 11

What is a common CF mutation in north europeans?

Answer 11

phe508del - 70% of N europeans

Question 12

What are common clinical features in CF? Adults and children.

Answer 12

In adults

• recurrent chest infections
• nasal polyps and sinusitis
• male infertility

Children

• recurrent chest infections
• failure to thrive

Question 13

What screening is done for CF?

Answer 13

Newborn bloodspot test on day 5
- Guthrie test

Initial screen of immuno-reactive trypsinogen
If positive, mutation analysis performed.
Screen positive referred sweat test

Question 14

What are accepted sweat chloride values (normal vs CF)?

Answer 14

> 60 indicative of CF

<29 (39 if age >6 months) = CF unlikely

Question 15

What are the two cardinal features of CF in children?

Answer 15

Pancreatic insufficiency leading to abnormal stools and failure to thrive.

Recurrent bronchopulmonary infection

Question 16

How is pancreatic insufficiency treated in CF?

Answer 16

Enteric coated enzyme pellets
High energy diet - not low fat
Fat-soluble vitamin and mineral supplements
H2 antagonist or PPI