cystic fibrosis Flashcards
ethnicity and CF
more common in European descent
What is CF?
- autosomal recessive genetic disorder
- mutation in a single gene on the long arm of chr 7
- most common mutation is the delta F508 (deletion, pehenylalanine at position 508)
- high salt concs in sweat (‘sweat test’)
- thick and sticky mucous becayse of lack of water
CFTR (mutation)
cyctic fibrosis transmembrane conductance regulator
diagnosis of CF
- newborn screening with ‘heel prick’ test - measure immunoreactive trypsinogen levels in blood
- genetic mutation analysis
- sweat test - measures the conc of chloride excreted in sweat (inc in CF)
problems CF causes in the body
- excessive salt loss in sweat
- OP
- growth retardation
- respiratory failure
- GI disorders
- infertility
pulmonary effects of CF
- impaired mucociliary clearance
- airways clogged with thick sticky mucous
- impairs clearance of microorganisms
- early colonisation of lungs with Staphylococci or H influenzae
- infections cause large inflam response
- act of neutrophils
- acc of debris from bacteria and neutrophils difficult to clear
- proteases of neutrophils damage airways
- cycle of infection & inflamm continues, lung fxn compromised
airway infections
- close monitoring of secretions (cough, swab, sputum culture)
- reg mon of lung fxn with spirometry, O2 sats
- without ABX can deteriorate quickly, fatal respiratory failire
- Tx threshold diff to no CF person
staphylococcus aureus
- usually initial infecting pathogen
- continuous prophylaxis as child
- minor exacerbations - oral flucloxacillin
- severe exacerbation - IV flucloxacillin or vancomycin
MRSA
- pt/family swabbed
- if in nasal - Tx with Mupirocin
- MRSA causing Sx - fusicid acid + rifampicin/trimethoprim, oral linezolid
- severe/acute exac - IV teicoplanin/vancomycin
haemophilus influenzae Tx
- oral amoxicillin
(if sensitive and no recent Hx of s/ aureus) - severe infections - chloramphenicol, cefuroxine (cephalosporin, tendonitis, seizure)
pseudomonas aeruginosa
- recurrent infections eventually lead to chronic colonisation
- chronic colonisation causes rapid decline in lung fxn
- pts have a 2-3 fold inc risk of death over 8yr period
exacerbations of P. aeruginosa
- treat early infections aggressively (attempt eradication)
- eradication regimens
eradication regimens for P aeruginosa
- 6 weeks ciprofloxacin and 3-6mth colistin
- 3 mths ciprofloxacin and colistin
- inhaled tobramycin (intol to ciprofloxacin and colitin or early regrowth of P aeruginosa or other Tx failed)
severe exacerbation, broad spec agets:
1. IV Tazocin
2. IV aminoglycosides (comb synergistic effect with beta latams)
caution with IV aminoglycosides (gentamycin, tobramycin)
nephrotoxicity
ototoxicity
nebulised antibiotics
- solution of drug into a fine spray
- inhaled, delivering the ABX deep into the lungs
- P. aeruginosa, reduce rate of lung deterioration and the number of IV courses needed
- colistin and tobramycin have been used
disadvantages of nebulised colistin and tobramycin
expensive
doxycycline - counselling
- sensitivity to sunlgiht
- swallow whole, remain standing
ciprofloxacin - counselling points
- interacts with milk, antacids, Fe, Zn
- risk of tendon rupture
- may induce convulsions (caution in epilepsy)
nebulised ABX - counselling points
- bronchospasm - prevent by taking with bronchodilator (salbutamol)
- 1st dose in hospital (measure lung fxn before and after)
- may need filter to prevent fumes in room
usual combination of ABX for CF infection
aminoglycoside + beta-lactam
When are macrolides used?
LT in pts with declining lung function, declining clinical status and chronic colonisation
eg of macrolide
azithromycin 250-500mg x3 WEEKLY
3 mucoactive agents
- rhDNase
- hypertonic saline (HS)
- mannitol dry powder for inhalation (Bronchitol 40mg)
rhDNase
rhDNase (dornase alpha, recombinant human deoxyribonuclease)
- CF sputum contains DNA derived from neutrophils
- aerolised rhDNase is an enzyme that cleaves DNA
- dec sputum viscosity and aid expectoration
hypertonic saline (HS)
ST:
- induce sputum in pts where upper airway cultures are -ve
- adjunct to physio
LT:
- mucoactive agent
- adjunct to physio
mannitol dry powder for inhalation (Bronchitol 40mg)
- mannitol = sugar alcohol
- inc hydration, aids clearance
- 400mg BD
aim for O2 sats
> 93%
NIV - non-invasive ventilation
- O2 therapy
- useful for airway clearance with physio techniques
- used LT, can improve gas exchange during sleep in mod/severe disease
vaccines in CF
- regular vaccines as per childhood
immunisation schedule - annual flu vaccination strongly recommended (pt & family)
- pneumococcal vaccination not required but offered if families prefer (not normally a problematic organism)
physiotherapy
- important for CF management
- physical exercise
- CV fitness = improved survival
- airway clearance techniques
- monitor MSK problems (posture, bone health)
lung transplantation
- option for end stage CF
- criteria: limited life expectanct (<2yrs) & severely impaired QoL
- 9yr survival post transplant
pancreatic insufficiency
- 95% of CF pts
- need pancreatic enzyme replacement and fat sol vitamins (A, D, E, K)
- more enzymes needed with fatty meal OR stools loose/frequent/oily/plale
- Creon 10,000 caps in childern/adults
CFRD - CF related diabetes
- most common co-morbidity in CF
- usually in adolecance/early adulthood
- destruction of insulin producint islet cells
- delayed and inufficient insulin secretion
- reduced insulin sensitivity
- Tx = insulin
- microvasculat complications develop
liver disease
- genetic cholangiopathy
- CFTR - expressed in liver, regulates fluid/electrolyte content of bile
- dec fxn results in biliary cirrhosis
- complications = portal hypertension, oesophageal varised, hepatic failure
bone health
- bone disease, low BMD
- delayed puberty
- steroid therapy
- CF related diabetes
- dec physical activity
- Ca & Vit D deficiency
- Vit K deficiency
- poor nutritional status
- chronic inflammaiton
fertility
- CBAVD - congenital absence of the vas deferens
- most male CF pts will be infertile (not all(
- normal fertility in females
- interactions with COC (rifampicin)
nutrition
- improved nutritonal status = better outcomes & survival
- poor body weight and height related to mottality
- daily energy requirements 100-150% of average for age
- high energy meals and snacks to achieve energy requirements and maintain weight
new therapies in CF
- Lumacaftor-ivacaftor (Orkambi) combination tablet
- lumacoftor = CFTR corrector, improves cellular processing
- ivacaftor = CFTR potentiator, inc probability the channel is open
- only if homozygous for F508del mutation
triple combination new therapy for CF
elexacaftor + tezacaftor + ivacaftor2
