Cystic Fibrosis

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management | Referral

Definition

Cystic Fibrosis (CF) is a genetic disorder that primarily affects the lungs, pancreas, and other organs. It results from mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, causing thick, sticky mucus production that leads to recurrent infections, malabsorption, and organ damage.

Aetiology

Cystic fibrosis is caused by mutations in the CFTR gene, located on chromosome 7. The most common mutation is F508del, which accounts for approximately 70% of cases. This mutation affects chloride and water transport across epithelial cells, leading to thick mucus production.

Pathophysiology

The defective CFTR protein leads to impaired chloride and sodium transport across cell membranes:

  • thick, sticky mucus builds up in the lungs, causing obstruction and recurrent infections.
  • in the pancreas, mucus blocks the ducts, leading to reduced enzyme secretion and malabsorption of nutrients.
  • in sweat glands, altered electrolyte transport leads to high chloride levels in sweat.

Risk Factors

  • family history of cystic fibrosis.
  • ethnic background: More common in individuals of Northern European descent.

Signs and Symptoms

Symptoms can vary but often include:

Respiratory:

  • chronic cough with thick sputum.
  • recurrent respiratory infections (e.g., pneumonia).
  • shortness of breath and wheezing.

Gastrointestinal:

  • steatorrhoea (fatty stools) due to pancreatic insufficiency.
  • failure to thrive in children despite adequate calorie intake.
  • abdominal pain or distension due to distal intestinal obstruction syndrome (DIOS).

Other:

  • salty-tasting skin (due to high chloride in sweat).
  • clubbing of fingers and toes (due to chronic hypoxia).

Investigations

Key investigations include:

  • Newborn Screening: this includes immunoreactive trypsinogen (IRT) test and genetic testing.
  • Sweat Test: this is the gold standard for diagnosis; elevated chloride levels (>60 mmol/L) confirm CF.
  • Genetic Testing: to check for specific CFTR mutations.
  • Sputum Culture: to identify pathogens such as Pseudomonas aeruginosa or Staphylococcus aureus.
  • Pulmonary Function Tests (PFTs): which shows an obstructive pattern (reduced FEV1/FVC).
  • Chest X-ray/CT Scan: which may reveal bronchiectasis or hyperinflation.
  • Faecal Elastase: to explore pancreatic insufficiency.

Management

1. Respiratory Management:

  • Airway Clearance: daily respiratory physiotherapy and postural drainage to remove mucus.
  • Inhaled Therapies:
    • Bronchodilators (e.g., salbutamol) to relieve airway obstruction.
    • Mucolytics (e.g., carbocisteine ) to reduce mucus viscosity.
    • Hypertonic saline to aid mucus clearance.
  • Antibiotics:
    • Oral or intravenous antibiotics for acute infections.
  • Long-term Oxygen Therapy (LTOT): for advanced disease with hypoxaemia.

2. Gastrointestinal Management:

  • Pancreatic Enzyme Replacement Therapy (PERT): e.g., Creon to aid digestion and nutrient absorption.
  • Vitamin Supplements: fat-soluble vitamins (A, D, E, K).
  • High-Calorie Diet: to address malnutrition and failure to thrive.

3. Advanced Therapies:

  • Lung Transplantation: for end-stage lung disease.

Referral

Consider referral to secondary care in the following scenarios:

  • Respiratory Specialist: for confirmation of diagnosis and management of lung disease.
  • Gastroenterologist: for persistent malabsorption or GI complications (e.g., DIOS).
  • Cystic Fibrosis Specialist Centre: for comprehensive, multidisciplinary care and access to advanced therapies.
  • Hospital Admission:
    • Acute exacerbations with severe breathlessness or hypoxaemia.
    • Recurrent chest infections unresponsive to outpatient treatment.
 
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