Embedded Files
Autosomal recessive multisystem genetic disorder affecting the CFTR gene, leading to thick secretions in the lungs, pancreas, GI tract, and other organs. Most common life-limiting genetic condition in Caucasian populations.
Autosomal recessive multisystem genetic disorder affecting the CFTR gene, leading to thick secretions in the lungs, pancreas, GI tract, and other organs. Most common life-limiting genetic condition in Caucasian populations.
Risk Factors
Positive family history (siblings, parents known carriers)
Caucasian ethnicity – especially Northern European descent
Carrier status in both parents (autosomal recessive inheritance)
Newborn screening positive for CF markers
Aetiology
Mutation in CFTR gene on chromosome 7, most commonly ΔF508 deletion
Defective CFTR protein impairs chloride and water transport across epithelial cells
Results in thick, viscous secretions in multiple organ systems
Pathophysiology
Abnormal chloride transport leads to thick mucus in lungs → airway obstruction, bacterial infection, bronchiectasis
Pancreatic insufficiency due to blocked ducts → malabsorption of fats and fat-soluble vitamins
Obstructed bile ducts → liver dysfunction
Obstructed vas deferens → male infertility
Sweat glands: salt not reabsorbed → salty sweat, risk of hyponatraemic dehydration
Chronic lung damage from infection and inflammation leads to progressive respiratory failure
Diagnosis
Usually detected on newborn screening
Sweat chloride test ≥60 mmol/L confirms diagnosis
Genetic testing for CFTR mutations
Clinical features: failure to thrive, chronic cough, greasy stools, recurrent respiratory infections
Meconium ileus at birth may be first sign in neonates
Nasal potential difference testing used in some specialised cases
Differential Diagnosis
Primary ciliary dyskinesia
Alpha-1 antitrypsin deficiency
Coeliac disease
Asthma or chronic bronchitis (older children)
Pancreatic insufficiency from other causes
Investigations
Sweat test – gold standard diagnostic test
CFTR genetic mutation panel
Faecal elastase to assess pancreatic function
Sputum cultures – monitor for chronic infection (e.g. Pseudomonas aeruginosa)
Chest X-ray or HRCT – bronchiectasis, hyperinflation
LFTs and liver ultrasound – monitor for hepatic involvement
Fat-soluble vitamin levels (A, D, E, K)
Pulmonary function tests – monitor disease progression
Management
Acute
Treat infective exacerbations with antibiotics (oral, IV, or nebulised depending on organism and severity)
Chest physiotherapy and airway clearance techniques (e.g. percussion, PEP devices)
Salbutamol or hypertonic saline to loosen secretions
Hospitalisation for severe exacerbations, oxygen therapy or NIV if needed
Chronic
Multidisciplinary care at a specialist CF centre
Regular airway clearance and chest physio
Long-term inhaled antibiotics for chronic infection (e.g. tobramycin for Pseudomonas)
CFTR modulators (e.g. ivacaftor, lumacaftor/tezacaftor/elexacaftor depending on genotype)
Pancreatic enzyme replacement therapy (CREON)
High-calorie diet with fat-soluble vitamin supplementation
Salt supplementation in hot weather or during illness
Bronchodilators and inhaled corticosteroids if bronchospasm
Management of comorbidities – CFRD (diabetes), liver disease, osteoporosis
Annual influenza and pneumococcal vaccination
Lung transplantation in end-stage disease
Complications
Respiratory: bronchiectasis, chronic colonisation (Pseudomonas), pneumothorax, respiratory failure
GI: distal intestinal obstruction syndrome (DIOS), liver disease, pancreatitis, gallstones
Nutritional: malabsorption, fat-soluble vitamin deficiencies, growth failure
Endocrine: CF-related diabetes, delayed puberty, infertility (especially in males)
Psychosocial: chronic disease burden, treatment fatigue, anxiety or depression
Multidrug-resistant infections
Progressive decline in lung function
Prognosis
Progressive, life-limiting condition, but improving with newer therapies
Median life expectancy now >40 years in developed countries
Early diagnosis, good adherence to multidisciplinary care, and CFTR modulators improve outcomes
Lung transplantation may extend life in advanced cases
Page updated
Google Sites
Report abuse