CPS 1.3 Cystic Fibrosis

  • Overview of Cystic Fibrosis (CF)

    • Definition: A life-limiting, autosomal recessive genetic disorder

    • Prevalence (UK): Incidence of 12500\frac{1}{2500} births.

    • Most common mutation: △F508\triangle F_{508}.

    • Genetic information: CFTR gene on chromosome 77; over 2,0002,000 mutations identified.

  • Inheritance and Genetics

    • Inheritance pattern: Autosomal recessive.

    • Carrier rate (UK): 125\frac{1}{25}.

    • CFTR gene location: On chromosome 77.

    • Mutational diversity: Over 2,0002,000 mutations identified.

  • Testing and Public Health Note

    • Cost to test a baby for Cystic Fibrosis: £1.50.

    • Question posed: Why isn't every baby tested? (Contextual campaign message).

  • Pathophysiology

    • Core issue: CFTR protein dysfunction

    • Affects chloride and water transport.

    • Result: Thick, sticky mucus accumulation

    • Accumulates in various organs.

    • Organs affected: Respiratory, gastrointestinal, endocrine, and reproductive systems.

  • Clinical Manifestations (Systemic)

    • Respiratory: Chronic cough, thick mucus, recurrent infections (Pseudomonas), bronchiectasis, nasal polyps, clubbing.

    • Gastrointestinal: Pancreatic insufficiency, malabsorption, meconium ileus, liver disease.

    • Endocrine: CFRD (Cystic Fibrosis-related Diabetes), delayed growth/puberty.

    • Reproductive: Male infertility (CBAVD), female subfertility.

    • Sweat glands: Salty sweat, dehydration, electrolyte imbalances.

    • Musculoskeletal: Osteopenia/osteoporosis.

  • General Multisystem Features and Malformations

    • Growth and nutrition: General growth failure due to malabsorption, vitamin deficiency (A, D, E, K).

    • Nose and sinuses: Nasal polyps, sinusitis.

    • Liver: Hepatic steatosis, portal hypertension.

    • Gallbladder: Biliary cirrhosis, neonatal obstructive jaundice, cholelithiasis.

    • Bone: Hypertrophic osteoarthropathy, clubbing, arthritis, osteoporosis.

    • Intestines: Meconium ileus, meconium peritonitis, rectal prolapse, intussusception, volvulus, fibrosing colonopathy, appendicitis, intestinal atresia, distal intestinal obstruction syndrome, inguinal hernia.

  • Manifestations by System (Expanded)

    • Lungs: Bronchiectasis, bronchitis, bronchiolitis, pneumonia, atelectasis, haemoptysis, pneumothorax, reactive airway disease, cor pulmonale, respiratory failure, mucoid impaction of the bronchi, allergic bronchopulmonary aspergillosis.

    • Heart: Right ventricular hypertrophy, pulmonary artery dilation.

    • Spleen: Hypersplenism.

    • Stomach: GERD.

    • Pancreas: Pancreatitis, insulin deficiency, symptomatic hyperglycemia, diabetes.

    • Reproductive: Infertility (aspermia, absence of vas deferens), amenorrhea, delayed puberty.

  • Diagnostic Methods

    • Sweat test: Chloride concentration

    • Child: abnormal if > 60 \,\mathrm{mmol/L} .

    • Adult: abnormal if > 90 \,\mathrm{mmol/L} .

    • Genetic testing: Confirming mutations in the CFTR gene.

    • Imaging: Chest X-rays for pulmonary involvement (hyperinflation, bronchiectasis), abdominal ultrasound for liver/pancreas issues.

    • Spirometry: Obstructive pattern.

  • Management Strategies

    • Approach: Multidisciplinary team (MDT)

    • Pharmacological treatments: Antibiotics, bronchodilators, pancreatic enzyme supplements (Creon).

    • Non-pharmacological treatments: Physiotherapy, nutritional support, and consideration of lung transplant.

  • Other Therapies (MDT) and Support

    • MDT members and roles: Physiotherapy, nutritional support, respiratory support, microbiologists, surgery, lung transplant, psychology, social care.

  • Psychosocial Impact

    • Emotional toll: On patients and families.

    • Challenges: Of chronic illness management.

    • Ethical considerations: In genetic counseling.

  • Advances in Research

    • Gene therapy prospects.

    • CFTR modulators: (e.g., Ivacaftor).

    • Screening programs: For early diagnosis.

  • Summary and Takeaways

    • Recap: Genetic basis, clinical presentation, diagnostics, and management.

    • Emphasis: Multidisciplinary approach.

    • Preparation: To develop a concept map in group work for CPS 1, Session 1.