Cystic Fibrosis

Question 1

what is the inheritance rate of cystic fibrosis?

Answer 1

1:2,500

Question 2

what does the gene mutation in cystic fibrosis affect?

Answer 2

the chloride ion channel that allows chlorine into the cell, CFTR.

Question 3

describe class one CFTR mutation

Answer 3

here there is no ion channel synthesis as the truncated mRNA gets binned

Question 4

describe class 2 CFTR mutation

Answer 4

here the mRNA goes on to produce abnormal protein that doesn’t go on to mature into a CFTR channel.

Question 5

describe a class 4 CFTR mutation

Answer 5

the CFTR produced is gated and doesn’t fully work

Question 6

describe a class 5 CTFR mutation

Answer 6

there is some incorrect splicing leading to a decrease in abundance of CFTR

Question 7

describe the function of CTFR

Answer 7

this is an active chlorine transport channel that regulates the liquid volume in the epithelial surface.

Question 8

what is the effect of defective CFTR?

Answer 8

there is reduced chlorine efflux and increased sodium influx. the cilia collapse due to the unregulated liquid volume on the epithelium and a build up of mucous layer causes lung damage.

Question 9

what are common symptoms of cystic fibrosis in infants?

Answer 9

> recurrent chest infection

> failure to thrive

Question 10

what are the common symptoms of cystic fibrosis in older children?

Answer 10

> recurrent chest infections
nasal polyps and sinusitis
male infertility

Question 11

what are the less common presentations of CF in neonatals?

Answer 11

> gut atresia
obstructive jaundice
vitamin deficiencies

Question 12

what are the less common presentations of CF in infants?

Answer 12

> rectal prolapse
> preudo-bartters syndrome
> anaemia
> oedema
> hypoproteinaemia

Question 13

what are the less common presentations of CF in adults?

Answer 13

> acute pancreatitis
liver disease
pseudo-barter’s
atypical mycobacteria

Question 14

what is the new-born screening for CF?

Answer 14

the Guthrie test and it is an immuno-reactive trypsinogen.

Question 15

what happens if the Guthrie test is positive?

Answer 15

a mutation analysis is performed and a sweat test to measure the chloride in sweat is performed

Question 16

describe the affect of CF on the pancreas?

Answer 16

pancreatic insufficiency creates pale, greasy, smelly stool because they cannot produce enough lipase so there is malabsorption of fat.

Question 17

how is the malabsorption of fat managed?

Answer 17

they are given a high energy diet and enteric coated enzyme pellets that are tailored to their diet. this is in conjunction with fat soluble vitamin and mineral supplements and proton agonists.

Question 18

as well as pancreatic insufficiency what is the other cardinal feature of CF?

Answer 18

recurrent broncho-pulmonary infection: pneumonitis, bronchiectasis, scarring and abscesses.

Question 19

what are the steps to prevent respiratory tract infection in early years?

Answer 19

> segregation
> air-way clearance and adjuncts
> mucolytics
> prophylactic antibiotics
>annual influenza vaccination

Question 20

what are the common organisms in respiratory tract infection?

Answer 20

> staph. aureus
haemophilus influenza
pseudomonas aeruginosa (later in life)

Question 21

what are the less common organisms in respiratory tract infection?

Answer 21

> burkholderia cepacia
stenotrophomonas maltophillia
alcaligenes xylosoxidans
atypical mycobacteria

Question 22

what is the management of chronic intermediate infection?

Answer 22

> suppress the bacteria load
treat the infective exacerbations
reduce inflammation

Question 23

what are the GI manifestations of CF?

Answer 23

> dysmotility:

> co-existent disease such as crohns and coeliac

Question 24

what are the bone manifestations?

Answer 24

> osteopenia (swollen fingers)

> arthropathy

Question 25

name some other manifestations of CF?

Answer 25

> hepatopathy
> upper airway polyps and sinusitis
> diabetes
> heat exhaustion
> bilateral absence of vas deferens
> vagina candidiasis

Question 26

what is the respiratory infection cycle that is created?

Answer 26

there is bacterial colonisation = inflammation = mucous plugging = airway ulceration and damage = bronchiectasis = bacterial colonisation = and so on

Question 27

what bacteria species infection increases with age?

Answer 27

pseudomonas aeruginosa

Question 28

what is pseudomonas aeruginosa acquired from?

Answer 28

> environment (particularly hospitals)

> other CF patients

Question 29

what is the colonisation of pseudomonas aeruginosa associated with?

Answer 29

> reduced life expectancy (28 vs 39 years)

> rapid lung function decline

Question 30

describe what happens to pseudomonas aeruginosa once it has colonised

Answer 30

it undergoes a mucoid change and forms a biofilm, micro-colonies in an alginate film so is protected from host defence mechanisms and rapidly acquires antibiotic resistance.

Question 31

how is a first infection of pseudomonas managed?

Answer 31

> oral ciprofloxacin and nebulised colomvcin

> IV ceftazidime and nebulised colomvcin

Question 32

what is associated with a colonisation of burkholderia cepacia?

Answer 32

> reduced life expectancy (16 vs 39 years)
rapid decline in lung function
cepacia syndrome: very rapid deterioation

Question 33

when does colonisation of stenotrophomonas maltophilia occur?

Answer 33

usually after pseudomonas infection but it can be a first gram negative infection

Question 34

what is mycobacterium abscessus resistant to?

Answer 34

all anti-tuberculosis chemotherapy

Question 35

what colonisations are contraindications for lung transplants?

Answer 35

> burkholderia cepacia

> mycobacterium abscessus

Question 36

for what species are oral antibiotic given?

Answer 36

> staph
haemophilus
pneumococcus

Question 37

for what species are iv antibiotics given?

Answer 37

> pseudomonas
stenotrophomonas
burkholderia

Question 38

how should you treat if the respiratory infection is multi resistant?

Answer 38

test for synergy between antibiotics and prescribe two antibiotics (beta lactam and aminoglycoside) in large doses to increase the volume of distribution for two weeks.

Question 39

how does ivacaftor help CF patients?

Answer 39

it is a CFTR protentiator that binds to CFTR and improves transport of chlorine ions.
> reduces sweat chloride
> improves lung function by 10%
> creates weight gain

Question 40

what gene mutation is ivacaftor effective?

Answer 40

patients with the celtic mutation (5-10% of patients)

Question 41

what are the indications for a lung transplant?

Answer 41

> rapidly deteriorating lung function
> FEV1 < 30% predicted
> life threatening exacerbations
> large weight loss
> hypoxia at rest
> estimated survival of 2 years

Question 42

what is the average survival of a lung transplant?

Answer 42

> 70-80% 5 years

> 50% at 10 years

Question 43

why are >95% of men with cystic fibrosis infertile?

Answer 43

absence of vas deferens

Question 44

how are male infertility issue managed?

Answer 44

> adoption
artificial insemination with donor sperm
intra-cytoplasmic sperm infection

Question 45

what are the absolute contraindications to transplant?

Answer 45

> other organ failure
> malignancy within 5 years
> significant peripheral vascular disease
> drug, nicotine or alcohol deficiency
> active systemic infection
> microbiological issues

Question 46

are the patients given active or palliative treatment at the end of their life?

Answer 46

this needs to be discussed with the patients and families. it is complicated due to transplantation issues and there needs to sensitivity about prolonging death rather than life.