Cystic Fibrosis

Question 1

What respiratory infection is common in children with CF? How do you treat it?

Answer 1

Psuedomonas aeruginosa = 80% colonisation by 25yrs old

Ciprofloxacin

Lots of Abx resistant strains

(also Mycobacteria)

Question 2

What is the aetiology and pathophysiology of CF?

Answer 2

Autosomal recessive condition – 1/25 people are carriers (estimated); ¼ chance that children wont inherit either gene, ½ will inherit one and be a carrier, ½ will inherit and have CF

CFTR protein:
A transport protein on the membrane of mucosal epithelial cells
Channel normally allows chloride ions out of the cells and into the lumen i.e. of the airway or pancreatic ducts
Malfunction leads to upset fluid transport – transport protein does not resorb Cl – Na is retained in the extracellular space because of a reduced electrical potential gradient across the membrane – decreased reabsorption of sodium from the fluid in the lumen – Na+Cl = salt that is then excreted in high quantities in the sweat of CF patients + reduced excretion of water (as water would normally follow the sodium but not with the salt)

Any system where this protein channel is present and dependent for the regulation of Na/Cl gradients will mean that these systems will have less appropriate (thicker) secretions and subsequently impact the function

Affects - resp, GI, hepatic, pancreatic, urogenital, skin, CNS, MSK

Question 3

What are some complications of CF?

Answer 3

Resp:
Nasal polyps, sinus infections, Bronchiectasis, Fibrosis, Pneumothorax

MSK:
Osteoporosis/paenia, clubbing

Endo:
Pancreatitis, CFDM (insulin resistant DM, no fasting hyperglycaemia)

Hepatic:
Gallstones, billiary cirrhosis (common cause of death), hepatic failure

GI:
Decreased motility, thick secretions, malnutrition, weight loss, reflux

GU:
Fertility problems (especially in men – will need help, but also in women), renal impairment

Question 4

How does CF typically present?

Answer 4

Often diagnosed on neonatal heel prick - newborns with a positive heel prick for CF, i.e. they have a raised immunoreactive trypsinogen (IRT) result, get a sweat test, which will be high if they have CF

Clinically:
75% present by age 2

Shortly after birth with a failure to pass meconium (may remain inside and become an obstruction = meconium ileus - 5-10% of CF - gross distension + bilious vomiting; mottled ground glass + dilated bowel AXR appearance, low fluid levels as meconium is viscous)

Rectal prolapse – 10%

Repeat, chronic or unusual lung infections

Vitamin deficiencies – ADEK

Salt loss syndromes

Question 5

How might someone present later?

Answer 5

Those diagnosed later (>18) – often with a milder mutation – lower rates of pancreatic insufficiency, diabetes and better lung function

Question 6

How do you investigate CF?

Answer 6

FHx +ve

Diagnosed on infant blood spot screening + sweat test + genetic testing +/- clinical manifestation of symptoms

Sweat test:
Higher Cl- in sweat

Genetic test:
CF producing abnormalities on both chromosome 7’s

Question 7

How do you mange CF?

Answer 7

Supplementation:
Pancreatic enzymes - taken with every meal 
Vits ADEK 
High calorie, high fat diet 
Possible insulin 

Resp:
Prophylactic Abx - Flucox (S.aureus), Amox (H.influenzae)
Inhalers - B2 agonists, ICS
Chest physio + special cough - at least 2x daily

Hepatic:
Vit K
Poss transplant

MSK:
Calcium (vit D + K)
Bisphosphonates
Exercise + PT

UG:
Infertility counselling +/- infertility treatment

Specialist nurses + MDT care to manage the complexity

Question 8

What is Lumacaftor/Ivacaftor (Orkambi)?

Answer 8

used to treat cystic fibrosis patients who are homozygous for the delta F508 mutation
lumacaftor increases the number of CFTR proteins that are transported to the cell surface

ivacaftor is a potentiator of CFTR that is already at the cell surface, increasing the probability that the defective channel will be open and allow chloride ions to pass through the channel pore