Cystic Fibrosis

• Cystic fibrosis is an autosomal recessive genetic condition affecting mucus glands - around 1 in 25 are carriers of the mutation
• Caused by a genetic mutation of the cystic fibrosis transmembrane conductance regulatory (CFTR) gene on chromosome 7
• The most common mutation of the CFTR gene is the delta-F508
• The CFTR gene codes for cellular channels, particularly a type of chloride channel
• Key complications:

  • Thick pancreatic and biliary secretions that cause blockage of the ducts - lack of digestive enzymes
  • Low volume thick airway secretions that reduce airway clearance - bacterial colonisation and susceptibility to infections
  • Congenital bilateral absence of the vas deferens in males
• Presentation:

  • Screened for at birth with the new born blood spot test
  • Meconium ileus is often the first presentation - meconium is thick and sticky, causing it to get stuck and obstruct the bowel
  • Meconium ileus presents as not passing meconium within 24 hours, abdominal distension and vomiting
  • If not diagnosed shortly after birth, it can present later in childhood with recurrent LRTIs, failure to thrive or pancreatitis
• Symptoms:

  • Chronic cough
  • Thick sputum production including haemoptysis
  • Recurrent respiratory infections
  • Steatorrhea - due to lack of lipase
  • Abdominal pain and bloating
  • Salty sweat
  • Poor weight and height gain
• Signs:

  • Low weight or height on growth charts
  • Nasal polyps
  • Finger clubbing
  • Course crackles and wheeze on auscultation
  • Abdominal distension
• Diagnosis:

  • New born blood spot testing
  • Sweat test - gold standard
  • Genetic testing for CFTR gene can be performed during pregnancy or as a blood test after birth
• • Normally the CFTR allows efflux of chloride and inhibits influx of sodium, keeping sodium and chloride in the lumen
  • In CF, more chloride leaves the cell and more sodium is reabsorbed along with water, so secretions are dehydrated and thickened with increased chloride
• Sweat test:

  • A patch of skin is chosen for the test and pilocarpine is applies
  • Electrodes are placed either side of the patch and a small current is passed between them
  • This causes the skin to sweat - the sweat is absorbed with gauze and sent to the lab for testing of chloride concentration
  • The diagnostic chloride concentration for cystic fibrosis is more than 60mmol/L
• Cystic fibrosis is a cause of bronchiectasis
• Imaging:

  • CXR - bronchiectasis, hyperinflation
  • HRCT - bronchiectasis, mucus plugging
• Cystic fibrosis patients are susceptible to microbial colonisation:

  • Common colonisers are staph aureus and pseudomonas aeruginosa
  • Pseudomonas colonisation leads to increase in morbidity and mortality
  • Can be treated with long term nebulised antibiotics and oral ciprofloxacin
• Management:

  • Chest physiotherapy
  • Exercise
  • High calorie diet- enteral feeding by PEG or NG tube may be needed
  • Creon tablets for pancreatic insufficiency
  • Insulin for pancreatic insufficiency
  • Prophylactic antibiotics
  • Bronchodilators
  • Nebulised DNase
  • Nebulised hypertonic saline
  • Vaccinations - pneumococcal, influenza and varicella
  • Fertility and genetic counselling
• History:

  • Respiratory - frequency of infections, cough, sputum, haemoptysis, breathlessness
  • Pancreatic - failure to thrive, steatorrhoea, thirst, polyuria
  • GI - abdominal pain, bloating, vomiting
  • Difficulty conceiving and irregular menstruation
• Lung function testing: an obstructive picture is most common but can be restrictive, mixed or normal
• Pancreatic insufficiency can be tested for with faecal elastase