Respiratory System >
Cystic Fibrosis (CF)
“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