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Cystic Fibrosis

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Overview

Cystic fibrosis (CF) is an autosomal recessive disorder mainly affecting the lungs, pancreas, liver, intestine, and reproductive organs characterised by increased viscosity of secretions. CF occurs due to a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7.

The main overall effects of CF are:

  • Thick airway secretions lead to reduced clearance and bacterial colonisation
  • Thick pancreatic secretions lead to blockage of pancreatic ducts and malabsorption
  • Congenital bilateral vas deferens absence in males leading to male infertility:
    • Sperm is still made, but cannot leave

The most common mutation in the UK is a delta-F508 mutation on the long arm of chromosome 7.

CF is screened for at birth with the newborn bloodspot test

Epidemiology

  • CF is the most common inherited disorder in Caucasian populations
  • CF affects 1 in 2500 births
  • The carrier rate of CF is 1 in 25

Presentation

  • Meconium ileus – may be the first sign of CF
    • Meconium is the first stool a baby passes within 24 hours. Failure to pass meconium within 48 hours is a red-flag suggesting an underlying disorder
    • Thick, viscous meconium may get stuck and lead to bowel obstruction and cause abdominal distention and vomiting
  • Recurrent infections – due to viscous, thick respiratory secretions and impaired clearance:
    • Chronic chough
    • Thick sputum production
  • Malabsorption and failure to thrive – due to viscous, thick pancreatic secretions and blockage:
    • Steatorrhoea – due to a lack of pancreatic lipase
    • Poor weight gain
    • Abdominal pain and bloating
  • Other features:
    • Nasal polyps
    • Short stature
    • Delayed puberty
    • Male infertility – due to congenital bilateral vas deferens absence in males
    • CF-related diabetes mellitus – due to digestion of the islets of Langerhans due to trapped pancreatic digestive juices, mimicking type 1 diabetes
    • Salty sweat – due to concentrated sodium and chloride in the sweat

Investigations

Overview

  • Newborn bloodspot testing – performed on all children shortly after birth
  • Sweat test:
    • The gold standard
    • Show abnormally high sweat chloride (>60 mmol/L)
  • Genetic testing;
    • May be performed antenatally via amniocentesis of chorionic villous sampling

Microbial Colonisation

Overview

Due to impaired clearance of viscous secretions in the airways, patients with CF may have bacterial colonisation in the lungs. Common organisms are:

  • Staphylococcus aureus – patients take long-term flucloxacillin prophylaxis to reduce the risk of infection
  • Pseudomonas aeruginosa – difficult to treat and worsens the prognosis of CF
  • Burkholderia cepacia – difficult to treat and worsens the prognosis of CF, contraindicates lung transplantation

Individuals with P. aeruginosa and B. cepacia should minimise contact to prevent cross-infection.

Differential Diagnoses

Primary ciliary dyskinesia

  • Although this can cause impaired airway mucus clearance and similar respiratory symptoms, there are no features of pancreatic insufficiency as the problem is with the cilia in the body, not the secretions themselves

Management

Overview

  • Lifestyle management steps:
    • At least twice daily chest physiotherapy and postural drainage
    • High-calorie, high-fat diet
    • Minimise contact with other people with CF who are colonised with P. aeruginosa and B. cepacia
    • Pancreatic enzyme and vitamin supplementation
  • Respiratory symptom management:
    • Prophylactic flucloxacillin:
      • Reduce S. aureus infection risk
    • Bronchodilators (e.g. salbutamol):
      • Helps with bronchoconstriction
    • End-stage respiratory failure:
      • Lung transplantation – contraindicated if chronic B. cepacia infection present due to rapid and severe declines in pulmonary function
  • CF-related diabetes:
    • Regular screening and insulin replacement
  • Gene-based therapies:
    • Lumacaftor/ivacaftor – if CF patient is homozygous for delta-F508 mutation

Monitoring

  • Patients are regularly followed up in specialists clinics every 3-6 months where they are monitored for complications

Complications

  • Chronic respiratory failure
  • Malabsorption and failure to thrive
  • Delayed puberty
  • Cor pulmonale
  • Liver disease
  • CF-related diabetes
  • Osteoporosis
  • Nasal polyps
  • Liver problems
  • Infertility

Prognosis

  • Estimated survival is around 45 years old before requiring lung transplantation

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