cystic fibrosis

Question 1

what used to be used as a diagnosis for CF in the past?

Answer 1

the sweat test

Question 2

what is CF?

Answer 2

• Autosomal recessive genetic disorder.
• Mutation in a single gene on the long arm of
  chromosome 7.
• The most common mutation is the ΔF508 (Δ = ‘delta’,
  = deletion, F = phenylalanine, at position 508.

Question 3

what is the CFTR action?

Answer 3

• In a healthy cell the CFTR ion channel will export chloride ions
• Changes in extracellular chloride then attracts water to the area which contributes to the low viscosity of mucus in the lungs
• CFTR mutation prevents Chloride export, water is not attracted to area
• Mucus becomes thick and sticky as a result of lacking water content

Question 4

what happens in the CFTR mutation?

Answer 4

• CFTR mutations vary in how they effect function
• Those leaving least function have the most profound effect.
• Mutations can be classed into 6 groups which relate to the mutation and residual function.
• This can be important in establishing prognosis and guiding treatment
• Where two different mutations are inherited, the gene for the mildest effect is dominant

Question 5

how do you diagnose CF?

Answer 5

• Newborn screening with the ‘heel prick’ test
  – Measurement of immunoreactive trypsinogen
  levels in blood
• Genetic mutation analysis
  – Diagnosis within 5 working days
• Sweat test
  – measures the concentration of chloride that is
  excreted in sweat. (elevated in CF)

Question 6

what are the symptoms of CF?

Answer 6

sinusitis
nasal polyps
excessive sodium in sweat
infertility
arthropathy
osteoporosis
growth retardation
respiratory failure
hepato-billiary disease
GI = diabetes, pancreatic insufficiency, intestinal obstruction= malnutrition

Question 7

what are the pulmonary effects of CF?

Answer 7

Defective ion transport causes airway surface liquid depletion resulting in impaired mucociliary clearance.
* Airways become clogged with thick sticky mucus which impairs the clearance of microorganisms.
* Often, early colonisation of the lungs with
* Staphlococci or H. influenzae

Question 8

what happens when there is a large inflammatory response in the airways?

Answer 8

• Recruitment and activation of neutrophils.
• Accumulation of debris from bacteria and neutrophils is more difficult to clear.
• Proteases from the neutrophils damage surrounding airways.
• Cycle of infection and inflammation and damage continues ultimately lung function is compromised

Question 9

what respiratory monitoring is done and why?

Answer 9

• Respiratory symptoms most common problem in CF
• Close monitoring of respiratory symptoms at every medical contact
  – Frequent microbiological surveillance of respiratory secretions – cough
  swab, sputum culture
  – Regular monitoring of lung function with spirometry and oxygen saturations

Question 10

what is the mainstay of therapy with airway infections?

Answer 10

• Antibiotics: mainstay of therapy
  – without patients may quickly deteriorate to fatal respiratory failure
• Treatment threshold different to unaffected people

Question 11

what is usually the initial infecting pathogen?

Answer 11

Staphylococcus aureus

Question 12

what do you give for exacerbations due to staph aureus?

Answer 12

• Minor exacerbations
• Flucloxacillin orally
• Severe exacerbation
• Intravenous (IV) Flucloxacillin or IV Vancomycin

Question 13

what is MRSA?

Answer 13

Methicillin Resistant Staphylococcus Aureus
(MRSA)

Question 14

how do you treat MRSA?

Answer 14

• Nasal carriage is treated with Mupirocin.
• If MRSA is suspected to be causing symptoms then
• Treat according to sensitivities
  – Fusidic acid + Rifampicin / Trimethoprim
  – Oral linezolid
• Severe acute exacerbation
  – IV Teicoplanin / Vancomycin

Question 15

How do you treat Haemophilus influenzae?

Answer 15

• Often amoxicillin orally
  – (if sensitive and no recent history of s.aureas)
• 20% of isolates now resistant – check sensitivity –
  most have beta-lactamase and will therefore be
  sensitive to co-amoxiclav.
• Severe infections
  – Chloramphenicol
  – Cefuroxine

Question 16

what is the impact of being infected with Pseudomonas aeruginosa

Answer 16

• Recurrent infections eventually lead to chronic
  colonisation
• Chronic colonisation causes rapid decline in lung function
• Patients have a 2-3 fold increased risk of death over 8 year period.

Question 17

how should you manage Exacerbations of P. aeruginosa?

Answer 17

• Treat early infections aggressively - attempt eradication
• Variation in eradication regimens used, examples include:
  – Six weeks of ciprofloxacin with between three and six months colistimethate sodium (colistin).
  – Three months of both ciprofloxacin and colistin
  – Inhaled tobramycin - only if intolerant to ciprofloxacin and colistin or early regrowth of P.
  aeruginosa or when other regimes failed.
• Following colonisation severe exacerbation management will involve broad spectrum IV agents.
  – IV Piperacillin-tazobactam
  – IV Aminoglycosides – used in combination, may have a synergistic effect with b-lactams.

Question 18

why may nebulised antibiotics be of use?

Answer 18

• Coverts a solution of drug into a fine spray.
• This can be inhaled, delivering the antibiotic deep into the lungs.
• IN CF patients with P. aeruginosa, reduce rate of lung deterioration and the number of IV courses needed
• Colistin and tobramycin have been used successfully

Question 19

what are the practical point to be aware of with the antibiotics used in CF?

Answer 19

• Doxycycline
• Sensitivity to sunlight.
• Swallow whole, remain standing.
• Ciprofloxacin
• Interacts with milk, antacids, iron, zinc
• Risk of tendon rupture
• May induce convulsions - care in epilepsy
• Nebulised antibiotics
• Bronchospasm – may be prevented by taking with inhaled
  bronchodilator
• First dose in hospital – measure lung function before and after
• May need filter to prevent fumes in room

Question 20

why should you use different combinations of antibiotics that have different MOA?

Answer 20

• Reduce the potential for bacterial resistance
• Benefit from their potential synergy

Question 21

what immunomodulatory macrolide is used d longterm in patients with declining lung function, declining clinical status and chronic colonisation?

Answer 21

• Azithromycin 250−500 mg 3 times weekly.

Question 22

what does the cochrane review do?

Answer 22

• Cochrane review
• Improve (forced expiratory volume in 1 second) FEV1 over 6 months.
• Doubled the rate of being free of exacerbations over 6 months
• Need for oral antibiotics was statistically significantly reduced
• Adverse effects uncommon

Question 23

what is the purpose of rhDNase?

Answer 23

• rhDNase (dornase alfa; recombinant human deoxyribonuclease)
  – CF sputum contains large amounts of DNA derived from neutrophils.
  – Aerolised rhDNase (Pulmozyme)is a synthetic enzyme that cleaves DNA
• used as a mucolytic to decrease sputum viscosity and aid expectoration.

Question 24

how can hypertonic saline be used?

Answer 24

• Hypertonic saline (HS)
  – Short term:
• to induce sputum in patients in whom repeated upper airway cultures are negative
• adjunct to physiotherapy
  – Longterm:
• as a mucoactive agent,
• adjunct to physiotherapy

Question 25

how does bronchitol work?

Answer 25

• Mannitol dry powder for inhalation - Bronchitol© 40 mg.
  – Exact mechanism unknown, mannitol is a sugar alcohol, likely it increases hydration of the pericilliary fluid layer, aiding mucous clearance.
  – Dose is 400mg (ten capsules inhaled via handheld device, twice daily)

Question 26

how do you treat hypoxia?

Answer 26

– Advanced pulmonary disease
– During pulmonary exacerbations when ventilation-perfusion mismatch may
result in oxygen desaturation.
* Oxygen therapy (acute admission)
– Routine intermittent oxygen saturation monitoring
– Aim to keep saturations ≥ 93%

Question 27

what is NIV?

Answer 27

– increasingly accepted as a therapeutic option
– useful for airway clearance in addition to conventional physiotherapy techniques
– Use long term – may improve gas exchange during sleep in moderate to severe
disease

Question 28

are patients with CF recommended to be vaccinated?

Answer 28

• Routine vaccinations recommended as per childhood immunisation schedule
• Annual flu vaccination strongly recommended for patient and family
• Pneumococcal vaccination not required but offered if families prefer
  – not normally a problematic organism

Question 29

how does physiotherapy help CF?

Answer 29

• Encourage and instruct on appropriate physical exercise
  – clinical benefit in many aspects of the disease process
  – cardiovascular fitness is associated with improved survival.
• Demonstrate and teach airway clearance techniques
  – Facilitates the removal of bronchopulmonary secretions improving
  ventilation
• Reducing airway obstruction
• Reducing airway resistance.
• Provide assessment and advice regarding inhalation therapy
• Monitor musculoskeletal problems (posture, bone health)

Question 30

when is lung transplant offered?

Answer 30

• Treatment option – end stage CF
• Transplant criteria
  – Limited life expectancy (< 2 years)
  – Severely impaired quality of life
• Transplant Assessment
  – Prognosis without transplant
  – Quality of life
  – Contraindications
  – Education

Question 31

how many people is affected by a pancreatic insufficiency?

Answer 31

• Affects 95% CF population

Question 32

how do you treat a pancreatic insufficiency?

Answer 32

• Pancreatic enzyme replacement and fat soluble vitamins (A,D,E,K) required
• Individualised dosing titrated to correct steatorrhoea, abdominal pain and decrease frequency and mass of stools.
• More enzymes may be needed with fatty meal or if stools are loose, frequent, offensive, pale and oily.
  – Creon micro (powder) infants
  – Creon 10000 capsules in children and adults

Question 33

when does CFRD usually occur?

Answer 33

• The most common co-morbidity in CF patients
  – Usually occurs in adolescence / early adulthood

Question 34

why does CFRD occur?

Answer 34

• Pathophysiology is complex.
• In some part due to the destruction of insulin
  producing islet cells.
• Delayed and insufficient insulin secretion.
• Also reduced insulin sensitivity.
• Treatment requires insulin therapy

Question 35

how does CFTR occur?

Answer 35

• CFTR
  – expressed on the apical surface of cholangiocytes and biliary epithelium.
  – regulates the fluid and electrolyte content of bile.
• Disrupted function results in progressive biliary cirrhosis
  – Complication include portal hypertension, oesophageal
  varices, ascites and hepatic failure.
• Management – as per obstructive liver disease

Question 36

how is bone health affected in CF?

Answer 36

• Bone disease and low mineral bone density
  – Delayed puberty
  – Steroid therapy
  – CF related diabetes
  – Decreased physical activity
  – Calcium and Vitamin D deficiency
  – Vitamin K deficiency
  – Poor nutritional status (poor weight gain)
  – Chronic inflammation

Question 37

how is fertility affected in CF?

Answer 37

• Due to congenital bilateral absence of the vas
  deferens (CBAVD)
• Most male patients with CF will be infertile (not all)
  – Counselling important
• Normal fertility in female patients
  – Contraception issues must be discussed
  – Consider interactions with combined oral
  contraceptive

Question 38

how does nutrition impact on CF?

Answer 38

• Improved nutritional status contributes to better outcome and survival
• Poor body weight and height independent predictors of morbidity and mortality in CF
• Daily energy requirements are 100-150% of the Estimated Average Requirements for age
• High energy meals and frequent snacks to achieve their energy requirements and maintain weight gain