Cystic Fibrosis

Cystic Fibrosis (CF) is a genetic disorder that primarily affects the lungs and digestive system. It’s caused by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, leading to the production of thick, sticky mucus that can clog airways and trap bacteria, resulting in repeated infections and lung damage.

  • Cause:
    • CF is an autosomal recessive disorder, meaning a person must inherit two defective CFTR genes, one from each parent, to develop the disease. Carriers, with only one copy of the mutated gene, usually do not show symptoms.
  • Diagnosis:
    • History (Hx):
      • Presenting symptoms in infancy or early childhood, including persistent cough, recurrent chest infections, poor weight gain despite a good appetite, bulky, greasy stools.
      • Family history of CF or unexplained infant deaths.
    • Examination (Ex):
      • Assessment for respiratory distress, wheezing, lung crackles.
      • Signs of malnutrition or poor growth.
      • Physical signs suggestive of chronic lung disease.
    • Investigations (Ix):
      • Sweat Test: Measures the amount of salt (chloride) in sweat; elevated levels are a hallmark of CF.
      • Genetic Testing: To identify mutations in the CFTR gene.
      • Chest X-rays and CT scans: To identify lung changes or damage.
      • Pulmonary Function Tests (PFTs): To assess lung function.
      • Stool Tests: To evaluate fat absorption.
  • Management:
    • Respiratory Management:
      • Airway clearance techniques to help loosen and clear mucus from the lungs.
      • Inhaled medications to open airways or thin mucus.
        • Dornase alfa
        • Hypertonic saline nebs (6% or 3%)
        • Mannitol dry powder
      • Antibiotics to treat lung infections.
        • Azithromycin for its anti-inflammatory effect
        • Tobramycin is common (Pseudomonas cover)
    • Gastrointestinal Management:
      • Pancreatic enzyme replacement therapy to help digest food.
      • High-calorie, high-salt, and high-fat diet to meet energy needs and support growth.
      • Vitamin and mineral supplements.
    • CF-Related Diabetes Management: Screening and management, as CF can affect the pancreas.
    • Physical Activity: Encouraged to improve lung function and overall health.
    • Lung Transplantation: In cases of severe lung disease.
    • New Therapies: Medications like CFTR modulators that target the underlying genetic defect in CF.
  • Monitoring:
    • Regular follow-up appointments to monitor
      • lung function
      • growth, and
      • nutrition.
    • Annual glucose tolerance tests to screen for CF-related diabetes.
    • Regular sputum cultures to monitor for lung infections.
    • Bone density scans as CF can lead to osteoporosis.

The approach to managing CF is multidisciplinary, involving pulmonologists, gastroenterologists, dietitians, physiotherapists, and other healthcare professionals. The treatment plan is often tailored to the individual’s needs, age, and disease severity. Advances in CF care have significantly improved the quality of life and life expectancy for individuals with this condition.

CFTR modulators are a group of medications designed to correct the malfunctioning protein made by the CFTR gene in Cystic Fibrosis (CF). These drugs target specific mutations in the CFTR gene, and their effectiveness depends on the type of CFTR mutation a person has. As of my last update, the following CFTR modulators are available:

  1. Ivacaftor (Kalydeco): This drug enhances the function of the CFTR protein once it reaches the cell surface. It’s effective in patients with specific CFTR mutations, such as the G551D mutation.
  2. Lumacaftor/Ivacaftor (Orkambi): This combination is used for patients who have two copies of the F508del mutation in the CFTR gene. Lumacaftor helps in moving the CFTR protein to the correct position on the cell surface, while Ivacaftor enhances its function.
  3. Tezacaftor/Ivacaftor (Symdeko/Symkevi): Similar to Orkambi, this combination also treats those with two copies of the F508del mutation or with one copy of the F508del mutation and a second mutation that responds to these medications.
  4. Elexacaftor/Tezacaftor/Ivacaftor (Trikafta/Kaftrio): This triple combination therapy is indicated for patients 12 years and older with at least one F508del mutation. It’s currently the most advanced CFTR modulator therapy and has shown significant improvements in lung function and quality of life for patients with CF.
  5. Others: Research and development of new CFTR modulators are ongoing, and more drugs are expected to become available in the future, expanding treatment options for a broader range of CFTR mutations.

It’s important to note that the availability of these medications may vary by country, and their use depends on the specific genetic mutations a person with CF has. Genetic testing is essential to determine which CFTR modulator, if any, is appropriate for a patient’s treatment.