Cystic Fibrosis

Question 1

What is the carrier rate and incidence of CF?

Answer 1

Carrier rate: 1 in 25. Incidence: 1 in 2,500 live births.

Question 2

What are the complications of CF?

Answer 2

Bronchiectasis (cystic and saccular), tenacious sputum, biliary obstruction and obstructive hepatitis, pancreatic dysfunction (endocrine - CFRDM [cystic fibrosis related diabetes mellitus], exocrine [excess fat in faeces]), infertility for males, psychological issues.

Question 3

Is CF autosomal recessive?

Answer 3

Yes.

Question 4

Describe how the trans-membrane conductance regulator doesn’t work in CF.

Answer 4

Chloride channel does not work properly, less chloride is pumped out and more sodium is let in so more water gets in. Leads to dry secretions.

Question 5

Describe the progression from CTFR DNA mutation to CF.

Answer 5

CTFR mutation -> altered protein -> ion transport -> altered secretions -> blocked ducts and impaired mucosal clearance -> infection, inflammation -> CF.

Question 6

What does CF cause?

Answer 6

Salty sweat, intestinal blockage, fibrotic pancreas, failure to thrive, recurrent bacterial lung infections, congenital bilateral abscence of vas deferens, filled sinuses, gallbladder and liver disease.

Question 7

Describe different types of defects in CFTR

Answer 7

Class I - no CFTR synthesis at all. II - CTFR trafficking defect, less CFTR gets to cell membrane. III - dysregulation of CTFR (diminished ATP binding and hydrolysis), IV - defective chloride conductance of channel gating. V - reduced CTFR transcription and synthesis.

Question 8

What is the CFTR?

Answer 8

Cystic fibrosis transmembrane conductance regulator.

Question 9

Give a common and uncommon mutation that causes CF.

Answer 9

Common - F508del. Uncommon - G551D.

Question 10

For a recessive disease, can you have different mutations in each copy of the gene?

Answer 10

Yes.

Question 11

Who gets tested for CF?

Answer 11

Anyone who had bronchiectasis under 40, upper lobe bronchiectasis, colonisation with staph, infertility or low weight gets a CF genetic test.

Question 12

How do people with CF miss getting diagnosed?

Answer 12

Don’t present, present out of hours, present sporadically, failure to think about it, loss of continuity in primary care.

Question 13

Describe some of the difficulties in treating CF.

Answer 13

Massive treatment burden (they take lots of medications), much treatment is preventative, complications can be rapid onset, when they feel sick they think it must be CF but it isn’t always.

Question 14

What is managed prophylactically in CF?

Answer 14

Antibiotics, pancreas, bowels, liver. Have a regular clinic review.

Question 15

What antibiotics are used in different CF infections?

Answer 15

Staph aureus - oral flucloxacillin and septrin. Pseudomonas - oral azithromysin; nebulised colomycin, tobramycin, aztreonam; inhaled tobramycin.

Question 16

How does CF cause pancreas exocrine failure and how is it treated?

Answer 16

Sludged up ducts, failure of secretion of lipases and amylase, digestive failure. Take CREON.

Question 17

How does CF cause pancreas endocrine failure and how is this managed?

Answer 17

Destruction of pancreatic islet cells, fatty replacement of pancreatic tissue. Have OGTT (oral glucose tolerance test) once a year and CGMS (continuous glucose monitoring), they usually need insulin as they have insulin production failure.

Question 18

What is distal intestinal obstruction syndrome (DIOS)?

Answer 18

Thick mucus blocks up the intestines, symptoms similar to constipation.

Question 19

What is the treatment for DIOS and how can you prevent it?

Answer 19

Treatment - gastrograffin, laxido and fluids. Prevention - laxido, hydration and keeping moving.

Question 20

What are the effects of CF on the liver?

Answer 20

Sludging up of hepatic ducts (intra and extra hepatic), portal hypertension (porto-systemic anastomoses, variceal bleeding, hepatic encephalopathy [causes disturbances of conscioussness]).

Question 21

What is the treatment of CF in the liver?

Answer 21

TIPSS (transjugular intrahepatic portosystemic shunt) (reduces anastomoses, reduction in bleeding risk, can increase encephalopathy risk).

Question 22

How can you manage an exacerbation of CF?

Answer 22

Antibiotics, physiotherapy (autogenic drainage, ACBT [active cycle of breathing technique], with and without physiotherapist), adequate hydration, increased dietary input (dietician).

Question 23

Why do you always give 2 antibiotics in CF?

Answer 23

To reduce resistance.

Question 24

What antibiotics do you give in CF?

Answer 24

Orals: augmentin, flucloxacillin, minocycline, septrin, fusidin, ciprofloxacin. IVs: for pseudomonas - tazocin, ceftazidime, tobramycin, meropenem, colistin. for staph aureus - flucloxacillin, tigecycline. For cepacia - temocillin.

Question 25

What are the benefits of giving the patient antibiotics at home?

Answer 25

Well tolerated, safe, saves money and keeps patients working.

Question 26

What does the G551D mutation do?

Answer 26

Normal CFTR, delivered to epithelium normally, non-functioning channel.

Question 27

What is ivacaftor and how does it work and what people will it benefit?

Answer 27

CFTR potentiator, improves chloride flow through the CFTR, people with G551D mutation.

Question 28

What drugs can be used to treat CF with the F508del mutation?

Answer 28

Lumacaftor.