CF Flashcards
CF stats
1/2000-1/2500 in Caucasian live births
1/25 carriers
>2000 possible mutations, different mutations causing different types of disease
most common CF mutation
delta F508 - CFTR (transmembrane conductance regulator protein) in chromosome 7
- this is also the most severe type and is associated with liver disease
what does CTFR protein do?
allows Cl- to flow out of the lung epithelium, letting Na+ flow in as a response. This will be followed by subsequent flow of H2O out of the cells, hydrating the mucous layer and on top and making it easy to clear by cilia.
without this, there would be abnormal transport of Cl-/Na+ and result in reduced airway liquid and sticky mucous –> shearing of epithelium, collapse of cilia layer and infection–>inflammation–>scar tissue, also reduces neutrophils activity due to reduced Cl- concentration.
but there is heterozygous advantage of increased resistance to salmonella and cholera
6 classes of CF mutations (class 6 not listed)
- 12%, G542X, no CTFR synthesis
- 87% (most common), delta F508, block in processing of CTFR protein
- 5%, G551Db, block in regulation
- 5%, R117H/D1152H, altered conductance
- 5%, 3849+10kbC–>T5T/A455E, reduced synthesis
3 stages of screening for CF
- antenatal
- neonatal
- postnatal
tests done in antenatal screening
(done after identification of CF in parents or sibling)
- preimplantation genetic diagnosis (from blastocyst)
- chorionic villus sampling (from placenta)
- amniocentesis (from amniotic fluid)
tests done in neonatal screening
- newborn blood spot day 5 (Guthrie test): if positive, refer to clinical assessment and sweat test
tests done for post natal screening
- sweat test: (if sweat chloride> 60mmol/L, high chance of CF 40-59, inconclusive <39 unlikely to be CF) - do faecal elastase test of confirm
10 systemic effects of CF
- pancreatic insufficiency effect
- recurrent bronchopulmonary infection
- type II diabetes
- osteoporosis
- pneumothorax
- haemoptysis
- finger clubbing
- arthropathy
- vasculitis
- bronchiectasis
effects of pancreatic insufficiency
might be useful to know that they normally secrete lipase which digests fat
- abnormal stool (pale, fatty, foul-smelling)
- failure to thrive (deficiency of fat soluble vitamins)
- diabetes
- classes 1-3 CF have pancreatic insufficiency while classes 4-6 have some pancreatic function (you actually only need 5% of the pancreas to be working to be asymptomatic)
recurrent bronchopulmonary infections effects
ex. pneumonia, bronchiectasis
- airways become stiff, dilated from chronic inflammation, would eventually result in obstruction, which leads to infection, scarring, abscesses.
(happens in a cycle)
causes of bronchopulmonary infections (side effects of nonfunctional CFTR protein)
- decreased mucociliary clearance from electrolyte and water transport problems, like with CGFR mutation (causes the cilia to become damaged)
- increased bacterial adherance to thick mucous
- shearing and infections caused by thick mucous against epithelium
- decreased encocytosis due to decreased neutrophil acitivity
progression of bronchopulmonary infections
progressive bronchietasis (this leads to infection) –> recurrent LRTI (begins to suffer from lung function) –> progressive airflow obstruction due to fibrosis and scarring (increasing exertional dyspnoea, survival related to FEV1)–> resp failure (nocturnal non invasive ventilation or even lung transplant needed)
4 CXR signs of bronchiectasis
- tramlines
- signet rings (cross section scans)
- mucous plugging
- consolidation
is finger clubbing present in CF?
YES
due to low O2 in the blood
this is also present in other diseases like CVS, liver, AIDS, inflammatory bowel disease
treatment of resp failure in CF (the cycle)
- mucous obstruction inflammation - treated with airway clearance via physiotherapy, mucolytics, bronchodilators
- infection - treated with oral/IV?neb antibiotics
- increased inflammation - treated with azithromycin
- fibrosis, scarring, bronchiectasis –> supportive treatment and management of symptoms
treatment of resp failure in CF
- mucous obstruction inflammation - treated with airway clearance via physiotherapy, mucolytics, bronchodilators
- infection - treated with oral/IV?neb antibiotics
- increased inflammation - treated with azithromycin
- fibrosis, scarring, bronchiectasis –> supportive treatment and management of symptoms
type II diabetes mellitus in CF
- body produces insufficient or ineffective insulin (90% of diabetes)
- can be treated with insulin in CF patients, normal hypoglycemics don’t work unlike normal ppl
- drug and diet low compliance (drug is <75% effective)
osteoporosis in CF
- failure to reach peak bone mass at 28 and accelerated bone loss in adulthood (after 34)
- excludes you from receiving lung transplant because a few weeks after the transplant, the bone mineral density would drop
- causes of osteoporosis includes: malnutrition, low BMI, steroids, vit D and K deficiency, septic, delayed puberty
pneumothorax in CF
- air accumulation in pleural cavity –> collapsed lungs
- chances of recurrence 50% in CF, 25% in nonCF
- affects 3-4% of CF patients
3 treatments for pneumothorax
- insert a chest drain
- collapse the pleural cavity through pleurodesis
- collapse the pleural cavity through surgery (peel away the parietal pleura from thoracic wall)
haemoptysis in CF
- bronchial wall destruction causes coughing up blood, and the blood vessels also becomes very leaky.
- minor blood streaking in 60% and major in 1% –> needs intervention
3 interventions for major blood streaking in haemoptysis in CF
- admission and resuscitation
- bronchial angiogram + embolisation (forming an embolism and stop bleeding)
- surgical resection
common and uncommon pathogens that are related to CF
COMMON: - pseudomonas aeruginosa (60-80%) - common in adults - haemophilus influenza (children) - staph aureus (children) - Burkhloderia cepacia (type III CF with bad prognosis) - stenotrophomonas maltophilia UNCOMMON - MRSA - aspergillus - M. abscessus (atypical mycobacteria)
treatment of pre-infections
Goal: eradication of early infection
- segregation to prevent cross infections
- mucolytics
- prophylactic antibiotics against staph aureus
- airway clearance and adjuncts
- annual infleunza vaccination
treatment of chronic infection
eradication is very hard at this stage
- suppress bacterial load
- treat symptoms of infective exacerbations
- airway clearance and adjuncts
- mucolytics
- prophylactic antibiotics for pseudomonas
what drug is used to reduce inflammation in infections
azithromycin
characteristics of pseudomonas aeruginosa (acquired where, affects on patients, etc.)
- reduced life expectancy and rapid decline of lung function
- HI and SA in children slowly replaced by this in adulthood
- quickly develops resistance to drugs by forming biofilms
- acquired from hospitals or other CF patients.
- let it be unless there is an exacerbation.
new drugs for CF
ivacaftor
orkambi: ivacaftor + lumacaftor
symkavi: ivacaftor +tezacaftor
(triple therapy just arrived, these drugs target different parts of CFTR protein synthesis that is blocked in CF depending on which type of CF it is)
these drugs do not cure CF, but improves QoL and reduces exacerbations
when do you need lung transplant?
- FEV1<30% predicted
- rapidly deteriorating lung function
- life-threatening exacerbation
- estimated survival < 2 years, or they will survive longer with transplant
- recurrent pneumothorax or recurrent haemoptysis
who is not eligible for lung transplant?
- ongoing infection
- end organ damage
- malignancy within 5 years
- inadequate social support
- drug, nicotine, alcohol dependency
- noncompliance with drugs
- steroids >20 mg daily
- osteoporosis (reduced bone mass)
- abnormal BMI
- low or high surgical risks
stats of lung transplant
30-40% die on waiting list
62% survives the first 5 yrs
52% survive 10 years
things that help improve QoL
(median survival 40 yrs)
- O2 and NIV
- exercise
- alternative therapies
- financial and mental support
- good nutrition
- advanced care planning
