Cystic Fibrosis in Children
Cystic Fibrosis (CF) is a serious, life-limiting genetic disorder inherited in an autosomal recessive pattern. In the UK, it affects about 1 in every 2,500 live births. The disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7, which codes for a protein that regulates chloride and water transport across cell membranes. A defective CFTR protein leads to the production of thick, sticky mucus, primarily affecting the respiratory, gastrointestinal, and reproductive systems.
Clinical Presentation
CF is a multi-system disease with a wide range of presentations that can change with age.
Neonates
Meconium Ileus: This is a key early sign, presenting as intestinal obstruction in a newborn due to meconium being too thick to pass.
Prolonged Jaundice: Due to liver involvement.
Failure to Thrive: Infants may not gain weight despite adequate feeding due to malabsorption.
Childhood
Respiratory: Children often experience recurrent respiratory infections, a chronic cough, wheezing, and nasal polyps.
Gastrointestinal: Symptoms include chronic diarrhoea, steatorrhoea (fatty stools), and poor weight gain due to pancreatic insufficiency.
Rectal Prolapse: This can occur due to chronic coughing and poor muscle tone.
Adolescence and Adulthood
As the disease progresses, more significant complications arise.
Respiratory: The most common cause of morbidity and mortality is progressive lung disease, which can lead to bronchiectasis, pneumothorax, and haemoptysis.
Gastrointestinal: Distal intestinal obstruction syndrome (DIOS) can occur. There is a risk of developing liver cirrhosis and portal hypertension.
Other: Cystic Fibrosis-Related Diabetes (CFRD), male infertility (due to absence of the vas deferens), osteoporosis, and arthropathy.
Diagnosis and Screening
Newborn Screening: All newborns in the UK are screened for CF via a heel-prick test on day 5 of life. This has led to earlier diagnosis and improved outcomes.
Sweat Test: This is the gold standard for diagnosis. A sweat chloride concentration of >60 mmol/L on two separate occasions is diagnostic of CF.
Genetic Testing: Analysis of the CFTR gene confirms the diagnosis by identifying specific mutations.
Other Tests: Faecal elastase can be measured to assess for pancreatic insufficiency. Imaging (chest X-ray) often shows signs of hyperinflation and bronchiectasis.
Management
CF management is complex and requires a multi-disciplinary team within a specialist UK CF centre. The goal is to manage symptoms, slow disease progression, and improve quality of life.
Respiratory Management
Physiotherapy: Regular chest physiotherapy is essential. Techniques include chest wall percussion, postural drainage, and the use of devices like the Flutter or Acapella to clear mucus from the airways.
Inhaled Therapies: Inhaled mucolytics (e.g., dornase alfa) are used to thin mucus, while bronchodilators may be used to improve airflow.
Antibiotics: Early and aggressive antibiotic therapy is crucial for respiratory exacerbations. Pseudomonas aeruginosa is a common and difficult-to-treat pathogen in CF, and management often involves nebulised antibiotics like colistin or tobramycin.
Immunisation: Annual influenza vaccination is vital.
Gastrointestinal Management
Pancreatic Enzyme Replacement Therapy (PERT): Oral pancreatic enzymes, such as Creon, are given with meals and snacks to aid in the digestion and absorption of fats and proteins.
Nutrition: A high-calorie, high-fat, and high-protein diet is crucial for maintaining a healthy weight.
Vitamin Supplementation: Fat-soluble vitamins (A, D, E, and K) are supplemented due to malabsorption.
Other Therapies
CFTR Modulators: These are a class of drugs that target the underlying CFTR defect. They are a significant breakthrough in treatment, with drugs like lumacaftor-ivacaftor and elexacaftor-tezacaftor-ivacaftor being used in the UK for specific mutations.