Cystic fibrosis

Question 1

Causes of CF

Answer 1

• autosomal recessive condition
  
  • chromosome 7
  • 1000 mutations found
  • most frequent = delta F508
• 1 in 2,500 births
• carrier rate = 1 in 25
• more common in Caucasians
• defective protein (cystic fibrosis transmembrane conductance regulator- CFTR)
  
  • c-AMP dependent chloride channel
  • found on membrane of cells

Question 2

Natural history of CF

Answer 2

• Average life expectancy has increased from a few years to mid-30s (current newborns 40 years)
• multi-system disorder
• abnormal ion transport across epithelial cells
• airway
  
  • ​reduction surface liquid layer
  • impaired ciliary function
  • retention of mucopurulent secretions
  • chronic endobrachial infections- Pseudomonas aeruginosa
• ​intestine
  
  • ​thick, viscid meconium produced
  • meconium ileus (10-20% infants)
• pancreatic ducts
  
  • ​blocked by thick secretions
  • pancreatic enzyme deficiency
  • malabsorption
• sweat glands
  
  • ​increased Na/ Cl in sweat

Question 3

Clinical features of CF

Answer 3

Gutherie test screening now picks up most CF

RESP

• reccurent chest infections
  
  • ​chronic
  • persistent, loose cough productive of purulent sputum
  • S. aureus
  • H. influenzae
  • 2” pseudomonas aeruginosa or Burkholderia
  • leads to damage of bronchial wall, bronchiectiasis and abscess formation
• O/E: hyperinflated chest (air trapping), coarse inspiratory crepitations +/- expiratory wheeze, finger clubbing

GI

• malabsorption
• maldigestion
• leads to failure to thrive
• steatorrhoea
• meconium ileus (10-20 % neonates)- vomiting, abdo distention and pailure to pass meconium

TEENAGE PRESENTATION

• diabetes mellitus
• hepatomegaly
• cirrhosis, portal HTN, LF (rare)
• intestinal obstruction
• increasing chest infections- often segregated advised not to socialise with other CFs
• pneuothorax, haempotysis
• females- fertile- tolerate pregnancy unless SEVERE LUNG DISEASE
• males- 100% infertile- lack of vas deferens- can father children through ICSI
• psychological

GENE THERAPY

Question 4

Treatment of CF

Answer 4

• Physiotherpy
  
  • ​Bidaily
  • Clear airway of secretions
  • Parents- taught airway clearance
  • Older children- breathing exercises, PT devices
  • Physical exercise effective and encouraged
• Prophylactic Abx
  
  • ​Flucloxacillin (PO)
  • ‘Rescue’ Abx if respiratory decline
  • IV ABx 14 days peripheral venous long line
  • Nebulised antipseudomonal ABx daily
  • Arithromycin- given to decrease resp. exacerbations, given regularly
• DNAse/ hypertonic saline nebs
  
  • ​thins secretions
  • may decrease no. of resp. exacerbations
• Central venous catheter
  
  • ​IV access difficulty
• Lung transplant​
  
  • ​bilateral sequential
  • end-stage CF lung disease
  • >50% survival at 10 years
• Oral enteric-coated pancreatic replacement
  
  • ​taken with all meals and snacks
• High calorie diet
  
  • ​>150% of normal calorie intake
  • overnight feeding gastrostomy
  • fat-soluble vitamin supplements
• Teenage
  
  • ​ursodeoxycholic acid improves bile flow
  • liver transplant
  • oral Gastrografin (intestinal obstruction)