Cystic Fibrosis

“Autosomal recessive mutation causing multisystem disease associated with abnormalities in salt and water transport across epithelial surfaces“

Risk Factors

• Modifiable: n/a
• Non-Modifiable:
  • Family history of CF
  • Known carrier status of both parents
  • White ethnicity

Aetiology

Mutation in the cystic fibrosis transmembrane regulator (CFTR) gene (commonest mutation is ΔF508)

Pathophysiology

For ΔF508: CFTR misfolds and can’t migrate to cell membrane → ↓ Cl­­- pumped out → ↓ negative regulation of ENac →  Na+ influxes into cell ® water drawn into the cell rather than to mucus →  mucus becomes desiccated and can’t be cleared by ciliary →  neutrophils recruited to clear bacterial colonisation.

Clinical Presentation

• Infant:
  • Failure to pass meconium and failure to thrive
• Adults:
  • Wet-sounding cough
  • Recurrent chest infections
  • Chronic sinusitis
  • Steatorrhea
  • Digital clubbing
  • Gastro-oesophageal disease

Investigations

• Bloods:
  • ↑ Immunoreactive trypsinogen
• Imaging: n/a
• Special:
  • Genetic testing – two mutated alleles
  • Sweat test – ↑ Cl^–

Management

• Conservative:
  • Chest Physiotherapy
• Medical:
  • Inhaled bronchodilators (salbutamol)
  • Inhaled mucolytics (dornase alfa, hypertonic saline)
  • Inhaled tobramycin
  • Anti-inflammatories (azithromycin, ibuprofen, prednisolone)
  • CFTR modulators (ivacaftor, lumacaftor)
  • Others: pancreatic enzyme replacement, fat-soluble vitamin supplementation, H2 antagonist/PPI (ranitidine/lansoprazole)
• Surgical: n/a

Complications

• Chronic respiratory acidosis
• Delayed puberty
• Chronic sinusitis
• Acute respiratory failure
• Cor pulmonale
• Distal intestinal obstructive syndrome
• Diabetes mellitus
• Nasal polyps
• Osteoporosis
• Advanced liver disease
• Acute/recurrent pancreatitis