Cystic fibrosis

Question 1

What is CF

Answer 1

• Most common genetic disease amongst white European populations. (seen in all ethnic groups)
• Each week 5 babies born with CF and 2 people die (CF Trust, 2014) •
• Result in defect in gene coding CF transmembrane conductance regulator (CFTR): a chloride channel
• CFTR expressed in epithelial cells of many organs ; resulting in a multisystem disease

Question 2

Clinical implication of CF

Answer 2

• Multisystem disease ; lungs, pancreas, intestine, liver, reproduction system
• Daily treatment
  
  • Physiotherapy
  • Nutrition
  • Medicines (oral, IV, Nebs)
• Life limiting disease
• No cure

Question 3

Background

Answer 3

• 1938 –described by Dr Dorothy Anderson pathologist at New York city babies hospital
• 1940s mucoviscidosis
• 1950s sweat test and antibiotics (Paul di Sant’Agnese)
• 1970s recognition of more CF possible abnormalities and treatment benefit
• 1989 gene identified

Question 4

Pathophysiology

Answer 4

• Autosomal recessive genetic disease: 1 in 25 people in UK unaffected carriers
• Distribution of mutations in population varies
• Screening for carrier status and antenatal diagnosis

Question 5

CFTR Protein

Answer 5

• Multifunctional protein regulating several ion channels
• 1480 amino acids
• A gated anion channel
• Regulates ion flux across cell membranes

Question 6

CF mutations

Answer 6

• 1000+ mutations described
• 75% caucasian UK F508del
  
  • Deletion of amino acid phenylalanine in position
• Efforts made to classify by particular genotype
• Mutation type doesn’t correlate well with lung function

Question 7

Diagnosis- Clincial features

Answer 7

• Failure to thrive (malabsorptionin GI)
  
  • Greasy stool
  • Large appetite
• Cough/recurrent respsymptoms
  
  • Abnormal chest shape, tachypnoea
• Meconiumileus(20%)
• Male infertility (absent vasadeferens)
• Diagnosis usually by 2 yrs of age
  
  • Can get late diagnosis

Question 8

Diagnostic tests

Answer 8

• Sweat test: gold standard for diagnosis
  
  • Interpretation: >60mmol/L Cl diagnositc
• CFTR mutation analysis
• Faecal elastase
  
  • Marker pancreatic function

Question 9

New born screening

Answer 9

• Performed through the Guthrie test carried out during first week of life
  
  • Immunoreactive trysin (IRT)
  • Mutation analysis
• Advantage with early diagnosis ieimproved nutrition in infancy
• Disadvantage ‐life limiting diagnosis during period of early bonding
• May identify “mildly affected” patients years before clinical suspicion
• New class of patients CFSPID • False positives/false negatives may still occur

Question 10

Management of CF-MDT

Answer 10

• CF Consultants/Doctors in training
• CF Nurse specialists (hospital and community)
• Ward nurses
• Physiotherapists
• Dietitians
• Respiratory Physiologists
• Pyschologists
• Social workers
• Other doctors (Liver, diabetes specialists etc)
• Pharmacists- prescriber role in outpatients and inpatients

Question 11

Manifestations of Cystic fibrosis

Question 12

CF Lung disease

Answer 12

• Aprox97% of CF deaths related to pulmonary causes
• Abnormal CFTR
  
  • leads to decreased airway surface liquid,
  • thick mucus
  • loss of ciliaryfunction
  • mucus plugging: infection
• Infections can occur from infancy

Question 13

Microbiology

Answer 13

• Organisms found in lower airways
  
  • Staphylococcusaureus
  • Haemophilus influenzae
  • Pseudomonas aeruginosa
    
    • Gram –ve rod. Older children (12‐19yrs old peak)
• Tests involve Sputum samples, cough plates, Bronchoalveolar lavage (BALs)
• Other organisms; MRSA, Burkholderiacepaciacomplex –opportunistic, Non tuberculousmycobacteria, Aspergillis: Allergic bronchopulmonaryaspergillosis

Question 14

CF Lung disease: treatment

Physiotherapy + Nutrition

Answer 14

• Lung function and survival correlate with nutritional status
• Immunity improves
• Muscle strength to clear secretions
• Reverse to cope with increased metabolic demands of exacerbation
• BMI <17 contraindication for lung transplant

Question 15

CF Lung disease: treatment
Antibiotics

Answer 15

• Prevent, eradicate and control infection
• High dose (Penetrate sputum, Altered pharmacokinetics)
  
  • Vd water soluble drugs increased ,
  • Increased renal clearance
• Oral, nebulised, IV
• Cultures guide choice
• Prophylaxis until 2yrs old : flucloxacillin

Question 16

CF lung disease: Drug treatments

Answer 16

• Mucus clearance
  
  • Inhaled bronchodilators (i.e. Salbutamol) pre physio
  • DornaseAlfa (Pulmozyme®)
  • Hypertonic saline (6% or 7%)
• Inflammation
  
  • InhCorticosteroids
  • Azithromycin
  • PO corticosteroids

Question 17

CF Pancreatic disease

Answer 17

• Aprox 85% of CF pts affected with pancreatic insufficiency
• Loss of pancreatic exocrine function (enzymes digest fat)
• Poor growth, steatorrhoea(fatty stools), diarrhoea, abdominal pain
• Tx‐replacement enzymes egCreon®
• Loss of pancreatic bicarbonate decreases small bowel pH
  
  • Add H2 antagonists or PPI
• Fat soluble vitamins ( vitA,D, E and ? vitamin K)
  
  • Malabsorptionimpair growth and development
  • Monitor on annual bloods