Cystic Fibrosis

Background/Epidemiology

• Most common fatal genetic disease in caucasians
• Incidence of ~1 in 2500 live births
• NB It can be associated with atopy/asthma in up to 88%

Genetics and Pathophysiology

• Result of mutations (most commonly ΔF508) affecting a gene on chromosome 7 encoding a subunit of a chloride channel (cystic fibrosis transmembrane conductance regulator- CFTR)
  • Results in increased sodium and chloride (salt) in sweat and increased resorption of sodium and water from respiratory epithelium.
  • The main pathology seen in CF is a relative dehydration of the airways which can predispose to bacterial infections and ciliary dysfunction
    • Chronic infections/dysfunction can result in bronchiectasis
  • There are other organs affected
    • e.g. pancreas, GI tract and reproductive system
• Most patients are identified through screening either antenatally (at risk) or at birth (screening)

Diagnosis

• The majority will be diagnosed by immunoreactive trypsinogen (IRT) on the blood spot (Guthrie) test 6 days post-natally

Complications/Clinical Features

• Most patients will develop bronchiectasis during childhood.
  • Lungs are ‘fragile’
    • Frequent exacerbations of bronchiectasis
    • Spontaneous pneumothorax (20%)
    • Haemoptysis
    • Nasal polyps
    • Respiratory failure
    • Cor pulmonale
    • Lobar collapse
• Extra-respiratory features include
  • GI
    • Malabsorption (including failure to thrive) and steatorrhoea
    • Biliary cirrhosis and portal hypertension
    • Gallstones
    • Acute pancreatitis
    • Heartburn and peptic ulcers (often secondary to pancreatic failure)
  • Diabetes (25%)
  • Delayed puberty
  • Male infertility
  • Stress incontinence
  • Osteoporosis
  • Arthropathy
  • Cutaneous vasculitis
  • Rectal prolapse (up to 10%)
    • NB ALL children who present with rectal prolapse in the absence of other symptoms should be investigated for CF

Management

• Patients require intense physiotherapy to help clear secretions from the lungs
• Regular nebulised tobramycin is used between acute exacerbations to help prevent/suppress chronic pseudomonas infection
• Patients will usually require intense (and possibly unusual) antibiotic treatments to tackle all infections (initially normal specific antibiotics for infections but later more specialised anti-pseudomonas antibiotics)