🔑 Key Learning

  • Most common inherited condition in Caucasians (1 in 2500 live births; 1 in 25 are carriers)
  • Autosomal recessive inheritance; caused by CFTR gene mutation (most commonly ΔF508)
  • Leads to thick, sticky secretions affecting lungs, pancreas, liver, GI tract, and reproductive system
  • Gold standard diagnostic test = sweat chloride > 60 mmol/L
  • MDT management essential: high-calorie diet, Creon, rhDNase, long-term antibiotics, and airway clearance

🧬 Pathophysiology

  • Mutation in CFTR gene (chromosome 7) → defective chloride channel → impaired Cl⁻/Na⁺ transport in exocrine glands
  • Resulting thick secretions → gland obstruction, inflammation, and organ dysfunction

👀 Clinical Features

Neonatal

  • Meconium ileus (bowel obstruction from thick meconium)
  • Vomiting, abdominal distension, delayed meconium

Infancy and Childhood

  • Failure to thrive, poor growth
  • Recurrent respiratory infections
  • Chronic productive cough
  • Steatorrhoea, bloating, constipation

Adulthood

  • Male infertility (vas deferens agenesis)
  • Female subfertility, increased ectopic pregnancy risk
  • Diabetes mellitus, chronic lung disease

🩺 Examination Findings

  • Clubbing
  • Nasal polyps
  • Fine crackles, wheeze
  • Obstructive spirometry pattern (↓FEV₁) - bronchiectasis 

🧪 Investigations

  • Newborn screening: Immunoreactive trypsin on blood spot
  • Sweat test (gold standard):
    • Chloride > 60 mmol/L = diagnostic
    • 30–59 mmol/L = indeterminate → genetic testing
  • Genetic testing to confirm CFTR mutation
  • Spirometry: Obstructive pattern

💊 Management

🫁 Respiratory

  • Airway clearance techniques + daily physiotherapy
  • rhDNase (dornase alfa) – breaks down DNA in sputum to reduce viscosity
  • Prophylactic flucloxacillin until age 3 (consider extending to age 6)
  • Long-term azithromycin for those with recurrent infections or declining FEV₁
  • SABAs (e.g. salbutamol) may help if bronchospasm present

🍽️ Gastrointestinal

  • Creon (pancreatic enzyme replacement) to manage malabsorption
  • High-calorie, high-fat diet
  • Ursodeoxycholic acid for liver involvement

📝 Exam Clues & Clinchers

  • Newborn with meconium ileus → CF until proven otherwise
  • Child with failure to thrive, steatorrhoea, chronic cough → CF
  • Diagnosis: sweat test > 60 mmol/L chloride
  • Long-term prophylaxis: oral flucloxacillin from infancy