cystic fibrosis Flashcards
1
Q
what used to be used as a diagnosis for CF in the past?
A
the sweat test
2
Q
what is CF?
A
- 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.
3
Q
what is the CFTR action?
A
- 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
4
Q
what happens in the CFTR mutation?
A
- 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
5
Q
how do you diagnose CF?
A
- 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)
6
Q
what are the symptoms of CF?
A
sinusitis
nasal polyps
excessive sodium in sweat
infertility
arthropathy
osteoporosis
growth retardation
respiratory failure
hepato-billiary disease
GI = diabetes, pancreatic insufficiency, intestinal obstruction= malnutrition
7
Q
what are the pulmonary effects of CF?
A
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
8
Q
what happens when there is a large inflammatory response in the airways?
A
- 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
9
Q
what respiratory monitoring is done and why?
A
- 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
10
Q
what is the mainstay of therapy with airway infections?
A
- Antibiotics: mainstay of therapy
– without patients may quickly deteriorate to fatal respiratory failure - Treatment threshold different to unaffected people
11
Q
what is usually the initial infecting pathogen?
A
Staphylococcus aureus
12
Q
what do you give for exacerbations due to staph aureus?
A
- Minor exacerbations
- Flucloxacillin orally
- Severe exacerbation
- Intravenous (IV) Flucloxacillin or IV Vancomycin
13
Q
what is MRSA?
A
Methicillin Resistant Staphylococcus Aureus
(MRSA)
14
Q
how do you treat MRSA?
A
- 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
15
Q
How do you treat Haemophilus influenzae?
A
- 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
16
Q
what is the impact of being infected with Pseudomonas aeruginosa
A
- 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.
17
Q
how should you manage Exacerbations of P. aeruginosa?
A
- 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.
18
Q
why may nebulised antibiotics be of use?
A
- 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
19
Q
what are the practical point to be aware of with the antibiotics used in CF?
A
- 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
20
Q
why should you use different combinations of antibiotics that have different MOA?
A
- Reduce the potential for bacterial resistance
- Benefit from their potential synergy
21
Q
what immunomodulatory macrolide is used d longterm in patients with declining lung function, declining clinical status and chronic colonisation?
A
- Azithromycin 250−500 mg 3 times weekly.
22
Q
what does the cochrane review do?
A
- 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
23
Q
what is the purpose of rhDNase?
A
- 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.
24
Q
how can hypertonic saline be used?
A
- 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
25
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)
26
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%
27
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
28
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
29
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)
30
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
31
how many people is affected by a pancreatic insufficiency?
* Affects 95% CF population
32
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
33
when does CFRD usually occur?
* The most common co-morbidity in CF patients
– Usually occurs in adolescence / early adulthood
34
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
35
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
36
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
37
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
38
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
