Cystic fibrosis

Cystic fibrosis (CF) is multisystem genetic disorder affecting the lungs, pancreas, liver, and intestines, characterised by production of thick, sticky mucus.

• Defective CFTR protein leads to impaired chloride transport across epithelial cells.
• Results in thick, viscous secretions in respiratory, gastrointestinal, and reproductive tracts.

Autosomal recessive inheritance of mutations in the CFTR gene on chromosome 7.

• Respiratory: Recurrent chest infections, wheeze, cough, dyspnoea, and sputum production.
• GI: Meconium ileus in neonates, pancreatic insufficiency, malabsorption, and steatorrhoea.
• Failure to thrive and malnutrition.
• Male infertility due to absent vas deferens.
• CF-related diabetes.
• Salty sweat.

• Cyanosis.
• Clubbing.
• Bilateral coarse crepitations.

• Sweat test: elevated chloride concentration is diagnostic.
• Genetic testing for CFTR mutations.
• Chest X-ray: bronchiectasis, atelectasis, and infiltrates.
• Pulmonary function tests: obstructive pattern.
• Stool elastase: to assess pancreatic function.

• Airway clearance techniques: physiotherapy, positive expiratory pressure devices.
• Inhaled bronchodilators.
• Mucolytics, e.g. rhDNase (dornase alfa; recombinant human deoxyribonuclease).
• Antibiotic therapy for respiratory infections (e.g., Pseudomonas aeruginosa).
• Oral pancreatic enzyme replacement to aid digestion.
• High-calorie diet with vitamin supplementation.
• CFTR modulator therapies for specific mutations.
• Lung transplantation in advanced disease.

• CFTR modulators are available depending on the CFTR mutation.
• They bind to the defective CFTR protein and increase the protein’s functionality.
• More efficacious when started in younger patients, conferring better prognosis.
• Example: Ivacaftor.

• Chronic respiratory failure.
• Cor pulmonale.
• Diabetes mellitus.
• Liver cirrhosis and portal hypertension.
• Distal intestinal obstruction syndrome.
• Complex/multi-drug-resistant infections, e.g. Burkholderia cepacia, MDR Pseudomonas, non-tuberculous mycobacteria, Aspergillus.

• Cystic fibrosis is an autosomal recessive disorder, with mutations causing a defective CFTR protein.
• Multiple systems are affected, causing susceptibility to chest infections, sputum production and  malabsorption.
• A sweat test showing elevated chloride concentration is diagnostic.
• Management is extensive for CF, including airway clearance, inhaled bronchodilators, mucolytics, pancreatic enzyme replacement and antibiotics (as required).
• CFTR modulators provide an advancement in treatment for those who can receive it.