Cystic Fibrosis

Multisystem genetic disorder with a heterogenous phenoytype affecting the CFTR channel, reducing chloride levels and ↑ viscosity of mucous across multiple organ systems, though most significantly in the lungs.

Epidemiology and Risk Factors

Pathophysiology

Changes to the CFTR gene alter chloride conductance through the CFTR channel.

Aetiology

Genetic disease:

  • Mendelian recessive inheritance
  • Heterozygotes are asymptomatic
  • Highly variable mutations and severity
    Over 1100 described mutations.

Clinical Manifestations

Multiorgan manifestations:

  • Respiratory
    ↑ mucous viscosity and ↓ mucociliary clearance, leading to:
    • Chronic sinusitis
    • Recurrent LRTI
      Chronic colonisation with atypical pathogens.
    • Obstructive lung disease
      Subsequent:
      • Bronchiectasis
      • Gas trapping
    • Chronic hypoxaemia
      • Cor pulmonale
  • MSK
    • Osteoporosis
      Impaired calcium absorption.
    • Impaired thermoregulation
  • GIT
    • Meconium ileus
    • Distal intestinal obstruction syndrome
    • Biliary obstruction
      • Biliary cirrhosis
      • Portal HTN
    • Pancreatic obstruction
      • Pancreatic exocrine deficiency
      • Diabetes
        Most common non-respiratory comorbidity.
  • GU
    • Male infertility

Diagnostic Approach and DDx

Diagnosis requires:

  • Clinical features
  • Laboratory evidence
    • Positive sweat test
    • CFTR gene abnormality

Investigations

Post-natal screening:

  • Trypsinogen
    High false-positive rate.
  • Sweat test
    Performed two weeks after birth.

Genetic testing:

  • Evaluates the 11 most common CF mutations
  • ~92% sensitive

Management

Medical management is primarily supportive:

  • Respiratory
    Aims to ↓ incidence and duration of respiratory tract infections. Includes:
    • Daily respiratory physiotherapy
    • Bronchodilators
    • Mucolytics
      e.g. Hypertonic saline.
    • Antibiotics
    • Anti-inflammatories
      Including inhaled or systemic corticosteroids, NSAIDs, and azithromycin.
    • CFTR modulators
      • Ivacaftor
        Potentiates chloride channel function in a large subset of CFTR mutations.

Surgical management:

  • Lung transplantation
    Requires bilateral due to suppurative disease.

Anaesthetic Considerations

Day surgery is usually inappropriate, but can be considered if:

  • Stable disease
  • Good baseline function

Preoperative investigations should include:

  • CXR
  • Bloods
    • FBE
    • UEC
    • LFTs
    • BSL
    • Coags
  • A
    • Airway choice
      • Spontaneous ventilation on LMA may reduce adverse GA effects on respiratory mechanics for short procedures
      • ETT facilitates tracheal suctioning and controlled gas exchange
      • Avoid nasal ETT where possible due to high incidence of nasal polyposis
    • Extubation early post-operatively
  • B
    • Obstructive lung disease
      Postoperative complications predicted by:
      • FEV1 ⩽60%
      • PCO2 >50mmHg
  • D
    • Volatile anaesthesia has greater bronchodilation than TIVA
  • E
    • Ensure complete reversal of neuromuscular blocker
  • C
    • Cor pulmonale
  • I
    • Requirement for isolation

Marginal and Ineffective Therapies

Complications

Prognosis

Poor prognostic factors include:

  • Pseudomonas colonisation
    • ↑ Rate of pulmonary decline
    • Recurrent infections
    • ↓ Survival
  • Pulmonary hypertension

Key Studies

References