cystic fibrosis Flashcards
what used to be used as a diagnosis for CF in the past?
the sweat test
what is CF?
- 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.
what is the CFTR action?
- 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
what happens in the CFTR mutation?
- 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
how do you diagnose CF?
- 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)
what are the symptoms of CF?
sinusitis
nasal polyps
excessive sodium in sweat
infertility
arthropathy
osteoporosis
growth retardation
respiratory failure
hepato-billiary disease
GI = diabetes, pancreatic insufficiency, intestinal obstruction= malnutrition
what are the pulmonary effects of CF?
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
what happens when there is a large inflammatory response in the airways?
- 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
what respiratory monitoring is done and why?
- 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
what is the mainstay of therapy with airway infections?
- Antibiotics: mainstay of therapy
– without patients may quickly deteriorate to fatal respiratory failure - Treatment threshold different to unaffected people
what is usually the initial infecting pathogen?
Staphylococcus aureus
what do you give for exacerbations due to staph aureus?
- Minor exacerbations
- Flucloxacillin orally
- Severe exacerbation
- Intravenous (IV) Flucloxacillin or IV Vancomycin
what is MRSA?
Methicillin Resistant Staphylococcus Aureus
(MRSA)
how do you treat MRSA?
- 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
How do you treat Haemophilus influenzae?
- 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
what is the impact of being infected with Pseudomonas aeruginosa
- 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.
how should you manage Exacerbations of P. aeruginosa?
- 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.
why may nebulised antibiotics be of use?
- 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
what are the practical point to be aware of with the antibiotics used in CF?
- 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
why should you use different combinations of antibiotics that have different MOA?
- Reduce the potential for bacterial resistance
- Benefit from their potential synergy
what immunomodulatory macrolide is used d longterm in patients with declining lung function, declining clinical status and chronic colonisation?
- Azithromycin 250−500 mg 3 times weekly.
what does the cochrane review do?
- 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
what is the purpose of rhDNase?
- 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.
how can hypertonic saline be used?
- 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
how does bronchitol work?
- 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)
how do you treat hypoxia?
– 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%
what is NIV?
– 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
are patients with CF recommended to be vaccinated?
- 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
how does physiotherapy help CF?
- 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)
when is lung transplant offered?
- 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
how many people is affected by a pancreatic insufficiency?
- Affects 95% CF population
how do you treat a pancreatic insufficiency?
- 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
when does CFRD usually occur?
- The most common co-morbidity in CF patients
– Usually occurs in adolescence / early adulthood
why does CFRD occur?
- 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
how does CFTR occur?
- 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
how is bone health affected in CF?
- 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
how is fertility affected in CF?
- 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
how does nutrition impact on CF?
- 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
