Cystic fibrosis

Question 1

What is your impression and goals of management?

• An 8-year-old boy presented to the emergency department after suffering from a kick to his right ribs during soccer practice. On chest X ray, you noticed some abnormalities, however no acute fractures. On further questioning, the mother tells you her son has been having frequent chest infections requiring oral antibiotics. He frequently has a wet cough and coughs up yellow/green sputum. His height and weight are tracking along the 5th centile and he is considerably shorter than his siblings and parents were at the same age.*
• OR*
• A 2 y/o presents with persistent cough for several months, associated with bulky frothy stools and feeding intolerance. Discuss how you would investigate and manage this patient.*
• OR*
• A 3-week-old has had a positive newborn screening test for CF and is said to be homozygous for CFTRF508 mutations. How would you confirm the diagnosis and counsel the parents on CF? What are the long-term outcomes?*

Answer 1

Impression → cystic fibrosis, an inherited chronic multi-system disease.

• Differentials*
• Primary immunodeficiency, primary ciliary dyskinesia, asthma (can co-exist), GORD, chronic aspiration, FTT, coeliac disease, protein-losing enteropathy
• Goals of management*

1. Targeted history and examination to identify CF symptoms and assess severity of the disease
2. Confirm the diagnosis with a chloride sweat test and genetic testing as required
3. Provide appropriate management with parental education and counselling and referral to a specialist centre with multidisciplinary support and regular monitoring

Question 2

Cystic fibrosis: history

Answer 2

History

• Symptoms
  
  • Respiratory → chronic cough, thick sputum production, recurrent RTIs, asthma
  • Gastrointestinal → meconium ileus (48 hours in neonate), steatorrhea and FTT (pancreatic disease), abdominal pain and bloating
  • Other → salty taste
• Antenatal history → complications, tests (amniocentesis and CVS → CFTR)
• Risk factors → family history
• Paediatric history → PMHx (newborn screening), recurrent infections, development and growth, vaccinations
• Complications of disease (if older) → respiratory exacerbations, bowel obstruction, pancreatic insufficiency (90%), diabetes (50%), liver disease (30%), infertility, osteoporosis

Question 3

Cystic fibrosis: examination

Answer 3

Examination

• General + vitals
• Growth parameters and developmental milestones
• Respiratory → crackles, reduced air entry, tachypnoea, use of accessory muscles, barrel chest, hypoxia, clubbing
• ENT → nasal polyps
• GIT → abdominal distension (obstruction), palpable faeces, rectal prolapse

Question 4

Cystic fibrosis: investigations

Answer 4

Investigations

• Screening
  
  • Newborn screening test → measures levels of immunoreactive trypsinogen in blood which is elevated in CF patients due to abnormal chloride channels in the pancreas; if >99th percentile, then screens for ΔF508 mutation
• Diagnostic
  
  • Chloride sweat test (quantitative pilocarpine iontophoresis) → increased Cl content in sweat (>60 mmol/L)
  • Genetic testing → 2 disease causing alleles of the CFTR gene; identify mutation genotype
• Other (+ those guided by presentation/complications)
  
  • Bedside → sputum culture, LFTs
  • Bloods → FBC (anaemia), EUC, LFT, BGL
  • Imaging → CXR
  • Other → faecal elastase (↓ in pancreatic insufficiency)

Question 5

Cystic fibrosis: counselling

Answer 5

Counselling

• Private quiet environment → consultant, social worker, both parents
• Gauge parent’s level of understanding
• Explain diagnosis and underlying pathophysiology and genetics
• Discuss key issues and complications
  
  • Issues → respiratory (infections, bronchiectasis, allergic bronchopulmonary aspergillosis), gastrointestinal (GORD, SBO, DIOS), pancreatic (insufficiency, diabetes), hepatobiliary (gallstones, cirrhosis)
  • Complications → pancreatic insufficiency (90%), diabetes (50%), liver disease (30%), infertility, osteoporosis
• Discuss prognosis → improving; median life expectancy 47 years
• Address parental concerns

Question 6

Cystic fibrosis: management

Answer 6

Chronic disease management

• Multidisciplinary team → respiratory, endocrine, GP, CF CNC, physiotherapy, dietician, pharmacist
• Prevention → preventing infections (hygiene etc.), vaccinations (influenza, pneumococcal, palivizumab [RSV])
• Monitoring for complications → respiratory exacerbations, pancreatic insufficiency, bowel obstruction. Specialist review every 6 months to monitor for bacterial colonisation and screening for diabetes, osteoporosis, vitamin D deficiency and liver failure
• Manage complications as needed
• Psychological and social support for patient and family

Specific management

• CFTR modulator therapy → ivacaftor
• Respiratory
  
  • Mucolytic agents → nebulised hypertonic saline, nebulised DNase (dornase alfa / pulmozyme), inhaled dry powder mannitol
  • Antibiotics → prophylactic flucloxacillin (s. aureus), inhaled tobramycin (pseudomonas), azithromycin (anti-inflammatory)
  • Salbutamol → helps with airway clearance
  • Chest physiotherapy
  • Exercise
  • Lung transplant → end stage respiratory failure
• Pancreas/GI
  
  • High calorie diet
  • Vitamin supplementation (esp. Fat soluble A, D, E, K)
  • CREON tablets → replace lipase enzymes
  • Aperients
  • Diabetes management
  • Liver transplant