Cystic Fibrosis Flashcards
what is cystic fibrosis (CF)
genetic disorder that affects mostly the lungs. Long-term issues: difficulty breathing and coughing up mucus as a result of frequent lung infections.
- common
What type of inherited condition is CF
autosomal recessive
What is the gene prevalence of CF? ie what is a person’s chance of having CF?
1:25
how many CFTR mutation classes are there
6
what fertility issues exist with CF in males
> 95% males infertile - blocked/absence of vas deferens (ducts that carry sperm before ejaculation)
what fertility issues exist with CF in females
may affect chances of conception even though they may have poor nutrition anyways
CF has no effect on _____ in males and women
sexual function
Intra-cytoplasmic sperm injection
intra-cytoplasmic sperm injection ICSI (single sperm cell is injected directly into the cytoplasm of an egg)
- only 25-30% success rate
- 3 attempts on the NHS
female fertility issues that need to be considered before trying through NHS (3)
screening of partner
counselling re long term impact of condition on family
need optimum health (lung function / weight)
does pregnancy affect the survival of women with CF
low numbers found in research/studies
what are some issues with lung transplantation?
it is the last resort treatment option- when things turn really bad
it doesn’t always work
no lung transplant centers in Scotland- have to travel to Newcastle
what is the criteria used to determine when patients require a transplant (6)
if their FEV1 is <30% weight loss hypoxia at rest or O2 levels dropping during exercise high CO2 levels recurrent worsening sepsis worsening QOL
what 5 categories/outcomes are possible for CF patients after team discussion about lung transplant possibility
put on active list - need transplant urgently
passive list- not emergency but probably require in future
too well
patient decides they don’t want to go through with it
team decide not to put patient on it
too ill - won’t cope with big surgery
what new list is there in the last 18 months or so within the NHS regarding lung transplant
ultra-urgent list - can be as quick as 24 hours
name some absolute contra-indications (reasons against) to transplant (6)
Other organ failure
Malignancy within 5 years
Significant peripheral vascular disease
Drug, nicotine, alcohol dependency - Newcastle won’t see anyone who has been smoking in the last 6 months
Active systemic infection
Microbiological issues (eg. M. abscessus- big worry)
which organism causing infection is worrying at the moment
M. abscessus - rapidly growing, multidrug-resistant NTM species that are found in soil and water
relative contra-indications to transplant? 2 or 3 needed to not go ahead with transplant (6)
Other organ dysfunction
Non-compliance
Steroids >20mg daily
Absence of recognised social support
Osteoporosis
Low BMI - anyone <18 won’t get transplant in Newcastle
Surgical risks (previous thoracic surgery)
what is the most common CFTR mutation class
dF508 70% N. europeans have this
what happens in class 1 CFTR mutations
synthesis of MRNA does not occur so no functional CFTR protein is made. This is due to non-sense mutation
what happens in class 2 CFTR mutations
CFTR protein is created, but misfolds, keeping it from
moving to the cell surface.
what is the normal function of CFTR protein
CFTR protein is created, moves to the cell surface and
allows transfer of chloride and water.
what happens in class 3 CFTR mutations
channel gate doesn’t open so no movement of water or Cl- ions
What happens in class 5 CFTR mutations
Normal CFTR protein is created and moves to the
cell surface, but there’s just not enough of it to function
What happens in class 4 CFTR mutations
CFTR protein is created and moves to the cell surface, but the function of the channel is faulty
in what ways can CFTR function be affected
if the movement of Cl- out of the cell is reduced then there can be a change in the concentration of fluid that bathes the cilia. Any change in this concentration or volume even can lead to cilial collapse, thick, sticky mucus or excessive inflammation
describe Cl- and Na+ movement when CFTR is mutated
Cl- efflux decreases
more Na+ is taken into the cell
how does cilial collapse lead to infection
the thick,sticky mucus that is no longer being beaten away starts to trap organisms this leads to recruitment of neutrophils and excessive DNA due to apoptosis performed by these neutrophils
how is CF picked up early in patients
through neonatal screening
what is the Guthrie test
newborn bloodspot at day 5 - can sometimes falsely diagnose or miss diagnosis however so not used on its own
describe what the chloride sweat test is
a neonatal screening technique for CF
the amount of chloride in sweat is measured and those with CF may have 2-5 times the norm amount of Cl-
key points of the UK CF screening algorithm
if no mutations are detected then you reanalyse
if one mutation is detected then after DNA analysis it could open up to other mutations
if two mutations are detected then you refer with presumptive diagnosis of CF
in what 2 situations can a positive screen result lead to an inconclusive diagnosis
if you have a norm Cl- with 2 CFTR mutations (on has unclear phenotypic consequences)
intermediate sweat chloride with 1 or no CFTR mutations - don’t know how they will turn out - some may develop CF some may not
what antenatal screening is carried out following identification of CF patient during pregnancy?
Pre-implantation genetic diagnosis - checking the genes or chromosomes of your embryos for a specific genetic condition
Chorionic villus sampling - sample of placenta to check if your baby has a genetic or chromosomal condition
Amniocentesis - sample of amniotic fluid to check if baby has genetic or chromosomal condition
then check any siblings to see if they have genetic condition
Management of CF
Specialist multi-disciplinary team due to multi-organ disease
Shared care with local clinics
Primary care - not as much involvement with GP because the vast doctor specialties required cannot be provided
Surveillance
Early treatment of infection
what are the 2 cardinal features of CF
pancreatic insufficiency (85-90%) - unable to break down food - abnormal stools - pancreas becomes fibrotic
recurrent bronchopulmonary infection
e.g pneumonitis, bronchiectasis, scarring, abscesses
abnormal stool signs
pale or orange
foul smell
greasy or oily
how is pancreatic insufficiency treated
enteric coated enzyme pellets (coated to avoid destruction in the stomach)
high energy diet
fat-soluble vitamin and mineral supplements
what is pancreatic insufficiency
inability of the pancreas to produce and/or transport enough digestive enzymes to break down food in the intestine and facilitate absorption of nutrients.
CF and failure to thrive
may thrive quite well on breast milk as it’s better than normal milk. May have deficiencies of fat soluble vitamins
describe the vicious cycle of CF
mucus obstruction inflammation (cilia collapsing) leads to infection (chronic)
this leads to more inflammation and then results in fibrosis, scarring and bronchiectasis
what therapeutic targets are used to prevent mucus obstruction inflammation
airway clearance physiotherapy -
dornase alfa - inhaled drug that breaks up DNA produced by neutrophils in the airways
hypertonic saline
how does hypertonic saline reduce mucus
it increases the amount of Na+Cl- in the airways. The salt brings water into the airways, which thins the mucus, making it easier to cough out.
what is used to treat increased inflammation due to the infection brought about from mucus obstruction?
azithromycin - an anti-inflammatory antibiotic
what main common organisms that cause infection in patients with CF (N.B. chronic condition means they’re prone to infection)
staph aureus and haemophilus influenzae - LRTI
pseuodmonas aeruginosa - most prevelant in adult years
less common organisms that cause infection in patients with CF
burkholderia cepacia
MRSA
ivacaftor CFTR modulator
helps people with CF who have class 3 gating mutations. - It binds to the defective protein at the cell surface and opens the chloride channel (holds the gate open) so that chloride can flow through, regulating the amount of water at the surface of the cell.
social, educational and economic impact on child and family
SOCIAL
- Barriers to making friends (seen as “different”) due to cough, missing school, different dietary requirement, taking “drugs”
- Increased depression/anxiety
- Low adherence to time-consuming treatments
- Hard on child if comparing with healthy siblings
- Increased costs to the family
- Time off work/Hospital attendances
- Financial benefits
why has treatment/management of CF gotten better? (6)
CF centres MDT teams Physio Nutrition/Enzymes Antibiotics Aggressive approaches
where is the CF gene?
on the long arm of chromosome 7
in which CFTR mutation classes is pancreatic insufficiency more common
Class 1, 2 and 3
what are the challenges for adults with CF
Transition - new MDT- adult is a bigger pool of people
prognosis
promise of new drugs
possibility of lung transplant
other conditions can develop- comorbidities arise
how do adults with CF present in clinic (5)
infertility bronchiectasis mild resp symptoms/recurrent LRTI (40%) hyperinflation clubbing
give examples of some other complications/conditions that CF can cause in the body due to being a multi-system disease (8)
diabetes haemoptysis pneumothorax osteoporosis male infertility pregnancy pancreatic insufficiency mec ileus - bowel obstruction
signs of CF in CT scans (4)
tramlines - dilated bronchial airways
signet rings - thickened bronchi walls
mucus plugging
consolidation
CF and type 2 diabetes
often see CF patients with type 2 diabetes due to certain issues
osteoporosis and CF
significant reduction in bone mass density in 1/3 CF patients and this may exclude you from being allowed a lung transplant
- in CF sometimes fail to reach peak bone mass in childhood and adolescence and then have accelerated bone loss in adulthood
- can occur due to malnutrition, steroids, delayed puberty, vit D/K defic
pneumothorax and CF patients
3-4% CF patients during lifetime
older you get, more severe obstructive lung disease
treatment same = chest drain, pleurodesis (mildly irritant drug into the space between your lung and chest wall), surgery
psuedomonas aeroginosa:
where are they acquired?
acquired from environment, other CF patients, segregation and disinfection policies
can cause reduced life expectancy
rapid decline in lung function
how does pseudomonas aeroginosa grow antibiotic resistance?
produces biofilm around toxins that antibiotics or macrophages cannot penetrate
non TB mycobacteria in CF
MAI, abscessus
mycobacterium abscessus
highly resistant
contraindication for transplantation
1 month in hospital then maintenance treatment for 1 year
how is pulmonary infection managed?
Treat early and aggressively with antibiotics
Oral antibiotics (eg Staph, Haemophilus, Pneumococcus)
IV antibiotics (eg PA, Stenotrophomonas, Burkholderia)
If multiply resistant, test for synergy between antibiotics
Large doses (increase volume distribution, increased clearance)
Two week courses
Indwelling subcutaneous ports (vascuports)
how much of a drug is lost using nebulised jet drug
about 50%
why might CF patients need bronchodilators for airway obstruction?
asthma/atopy
- Bronchial Hyper Reactivity in 40% CF patients
bronchial plugging, inflammation - bronchial wall thickening
chest physio
autogenic drainage, active cycle of breathing, huffing
airway oscillating devices (PEP- mask that helps you breath better)
mucolytics: function and examples
reduce viscosity of phlegm making it easier to cough it up
pulmozyme
hypertonic saline
bronchitol
how does azithromycin work as anti-inflammatory drug
it reduces biofilms produced by bacteria
ways of improving quality of life of CF patient
double lung transplant
oxygen and non-invasive ventilation exercise support advanced care planning DNAR - do not attempt resus
