Cystic Fibrosis in Children and Adults Flashcards
What type of genetic disease is CF?
Autosomal recessive
What is the difference between recessive and dominant diseases. Which is homozygous and which is heterozygous?
recessive means you need 2 faulty alleles, one functioning allele is enough to maintain normal functioning, however, if 2 mutant alleles are present (homozygous state), there are no healthy alleles so disease is present.
Whereas when it is dominant, the faulty allele overides the funtioning allele and causes disease with just one faulty set of genes. This means that genetic disorders can occur in heterozygous state.
Is CF the most common autosomal recessive disease? What proportion of people are carriers?? Most common mutation? What causes death?
Yes
1 in 25 are carriers in the UK
Most common mutation is deltaF508
Most common cause of death is respiratory failure
What are the chances of being affected/carier/unaffected if m+d both arecarrier?
- 25 completely unaffected and inherit 2 healthy genes
- 5 carriers - 1 healthy and 1 mutated
- 25 affected with condition
What happens to the transmembrane conductance regulator protein (CFTR) in CF and what are the effects of it? Which chromosome codes the CFTR protein?
The transmembrane conductance regulator protein (CFTR) is either blocked/partially blocked, basically doesn’t allow CL- ions through.
This means in sweat glands (for example) both Cl- and Na+ are completely sweated out of the body (Na+ has opposite charge and is pair of Cl-).
In the lungs it traps the Cl- within the cell, Na+ and H20 follow into cell. Causing the mucus to become extremely sticky as it is dehydrated and missing/has a reduced airway suface liquid layer. This can lead to shearing and impaired bacterial killing via neutrophils.
The protein is coded for on chromosome 7
How many mutation classes are there? Which classes cause severe disease/mild disesae? Which is most common disease type?
more than 2500 mutation classes.
Types 1-3 are completely dysfunctional and so cause severe disease
Types 4-6 have some function and so cause mild disease.
Most common is Delta F508 which is Type 2. Type 2 account for 75% all CF cases.
When is antenatal testing done and what tests are done?
With baby in womb following identified parent/sibling with CF.
Tests include:
Pre-implantation genetic diagnosis
Chorionic villous sampling
Amniocentesis (Amniotic fluid)
What is the Guthrie test?
A simple heel prick blood test for CF done on day 5 after birth.
What is a sweat test and when is it done?
Done after a positive Guthrie test and on day 5,
Measures concentration of chloride in sweat. Less reliable in infants under 6 months and in adults.
Nb a faecal elastase can also be done to measure gut absorption.
Sweat chloide levels for diagnosis
Over 60 mm/L is abnormal - high chance of CF
30-59 = inconclusive
30 and below probably not CF.
Usually repeated to confirm
What is SPID?
screen positive inconclusive diagnosis - chloride and genetic analysis don’t match, grey area.
(Normal sweat chloride with 2 CFTR mutations
Intermediate sweat chloride with 1 (or no) CFTR mutations)
Is CF a multisystem disease?
yes
2 common presentation of CF?
pancreatic insufficiency and lungs (infection and bronchiectasis)
What does the pancreas do ususally? How can this be affected in CF and which enzymes are affected?
Release enzymes to break down food.
Most people with CF do not make pancreatic enzymes. The pancreatic duct cells also secrete bicarbonate into the intestine to neutralize stomach acid via the CFTR channel. The inability to neutralize stomach acid contributes to malabsorption in many cf patients.
Enzymes are trypsin and colistin
What is the effect of the lack of enzymes (trypsin and colistin) in CF?
Malabsorption
Abnormal stools - pale, offensive, float
Failure to thrive
Which classes are insufficient pancreatic? What % function do you need, so why may CF patients be asymyptomatic?
1-3 produce no pancreatic enzymes, types 4-6 produce some, which is enough to hit the 5% needed to function, so they may be pancreatically asymptomatic.
What is the second common presentation of CF throughout life? What can underlying causes be be caused by?
Recurrent bronchoplumonary infection. pneumonia Bronchiectasis Scarring Abscesses
What are “tram lines” and what are they most likely to be a result of?
They’re fat tram lines on a CT of a patients lung, caused by bronchiectasis (widening of the bronchioles), caused by recurrent infections and scarring in CF.
What is the airway surface layer?
The layer of watery substance that sits on top of the cilia in the respiratory tract and helps keep everything flowing (up the way)
Why does pulmonary infection occur? (what does the CFTR abnormality cause?
Abnormal electrolyte transport across cell membrane
Dehydration of airway surface layer (water later which allows mucous to slide easily up airway to be coughed up)
decreased mucociliary clearance
Mucous sticks to mucosal surface and causes shearing and inflammation
decreased access to bacteria
decreased bacteria killing
How does bronchiectasis occur?
you get reduced mucociliary clearance, increased bacterial adherence to the mucosa and reduced killing of bacteria. As a result, you get bacterial colonization within the mucus that causes inflammation, mucus plugging, Airway ulceration and airway damage, and ultimately bronchiectasis.
how much sputum can a CF patient cough up in a day?
Several cups a day!!
Survival related to what
Lung function (FEV1)
What would you see on a ct with cf?
Tram lines, signet rings (big brinchiOle O with vessel next to it), mucous plugging and potentially some consolidation (infection)
What are signet rings?
big brinchiOle O with vessel next to it
do CF get clubbing?
yes, they can
Who might be in the MDT? Why do CF patients need a vast MDT and shared care?
A large amount of people!
Physician Nurse specialist Physiotherapist Dietician and Diabetologist Psychologist Pharmacist Lung function physiologist/technician Microbiologist Gastroenterologist
As well as Primary care:
Surveillance
Early treatment of infection
What do physiotherapists/dieticians help with?
Physios can help people cough up all the excess mucus (clear their airways), and dieticians can help make sure they are getting enough nutrients, manage bowel issues and diabetes.
Microbiologist why?
Because CF patients often end up with funky bacteria and so to check them out and get them on the right antibiotics.
How to treat pancreatic insufficiency in CF?
Replacement enzymes (CREON)
Diet (High energy, NOT low fat), maybe calorie supplement drinks)
Nutritional Supplements - Fat-soluble vit and mineral supplements.
How many creon tablets(replavement enzymes pancreas) might a patient need to take?
30-40 per day! So will take a handful with a meal
What diet would a CF patient have?
Calorie rich high energy!
What nutitional supplements would be given?
Fat Soluble vits and minerals
How do we treat the mucus obstruction and inflammation found in patients with CF?
mucolytics (oral/inhaled thin out mucus) eg hypertonic saline
bronchodilators (eg salbutamol)
steroids
How do we treat chronic infections?
ANTIBIOTICS!!
What can be used to help with increased inflammation and why is this amazing?
Azithromycin - great as has antibiotic and anti inflammatory properties! Can be taken long term at a low dose.
When at fibrosis/scarring/bronchiectasis stages what would you do to help?
Support:
Oxygen
NIV (non invasive ventilation)
Psychological support
Social issues eg benefits
Is the type and management of diabeties in CF the same as in non CF patients?
no
Which type more common in CF?
Type 2 diabetes
Difference type 1 vs type 2 diabetic and which type are more common in CF?
Type 1 - autoimmune disease, no insulin made
Type 2 - Not enough /ineffective insulin.
Difference CF diabetics/normal diabetics
Normal Diabetes usually need to control their diet, whereas in CF they need a high calorie diet (compliance is a major problem). Insulin is a benefit in CF compared to non-CF who benefit from oral drugs.
What happens to Bone mineral density (BMD) in patients with CF? What are the risks and treatment?
Decreases, the sicker you are the worse it gets.
Risks are fractures
Treatment is weight bearing exercise, bone protection drugs
If gets to osteoporosis stage not able to offer lung transplant as you are on heavy steroids following the transplant which will decrease the bone density further.
What are the predictors of low BMD?
Bad other things. (The sicker you are the worse it gets) Low FEV1 req antibiotic courses Steroids Low BMI / malnutrition Low exercise Age Male Diabetes Vit D / deficiency Delayed Puberty
What % patients will have a pneumothorax? When is it more likely to occur? Treatment?
3-4% more likely in older patients with more severe obstructive lung disease. Recurs in 50% of patients. Same treatment as non-cf - chest drain/aspiration.
Why does Haemoptysis occur in CF?
Leaky blood vessels in infections.
What is minor hymoptysis and how common in CF?
60% patients can have this, blood streaking.
What classifies as a MASSIVE hyoptysis and how common in CF?
May be preceded by gurgling in chest, you would admit, resuscitate. may need bronchial angiogram and embolisation. 1% patients every year.
Why does minor hymoptysis increase with chest infections?
Because the blood vessels become more leaky.
What are the risk factors for haemoptysis?
Severity of CF
High no. excacerbations
Fungal lung infection
Blood thinners (liver disease, vit K deficiency, anticoagulants)
DO children change MDT team as they progress to adults? What can be discussed in a meeting on moving teams?
Yes, they have transition clinics.
Key discussions include: Wish for a family Large number of drugs, compliance Missing work Restrictions on careers and hobbies Transport costs Promise (and cost) of new drugs Media/Social media pressure and misinformation Now aware of prognosis Possibility of lung transplant Cross infection Other conditions develop: Diabetes, liver disease, osteoporosis, fertility issues, haemoptysis, mental health issues – can develop anything else not related to CF
When can new modulator drugs be prescribed? What drug is looking to be the most promising drug so far? How do they work?
If there is the corresponding gene mutation is present. KAFTRIO is the most promising so far. Address different parts of CFTR production, processing, folding, transport and insertion into the membrane.
Small benefits in lung function. More significant benefit is fall in chest exacerbations, rise in weight and improved QOL.
Why a double lung transplant is given? And what circumstances would lead to a lung transplant?
A single one isn’t given as the infection from the current lung can go and infect the new one.
Rapidly deteriorating lung function FEV1 < 30% predicted Life threatening exacerbations Estimated survival <2 years Other: recurrent pneumothorax, recurrent severe haemoptysis
What % patients die on waiting list for lung transplant? What is the survival rate at 5 years and then again at 10 years?
30-40%, survival rate is 62% and 52% at 5 and 10 years respectively.
what 3 questions should be thought about before referal onto waiting list for lung transplant?
Are the lungs bad enough
Is the rest of the body good enough
Does the patient want to take the gamble?
What can be contra-indications for lung transplant?
Osteoporosis Malignancy Some bugs (Burkholderia Cenocepacia genomovar 111, mycobacterium Abcessus) Other organ failure Significant peripheral vascular disease Drug, nicotine, alcohol dependency Active systemic infection
Which microbiological issues would be contraindications for transplant?
Burkholderia Cenocepacia genomovar 111, Mycobacterium Abcessus
What are some relative contraindications for transplant when you have to use your own judgement?
Other organ dysfunction Non-compliance Steroids >20mg daily Absence of recognised social support Osteoporosis Low or high BMI Surgical risks (previous thoracic surgery) Pscyhological instability
What is the BMI cut off for lung transplant?
less than 17 and greater than 30
What is the most crucial factor in determining if survival will be decreased or the median of around 40?
If not colonised by bacteria, median survival is around 40. If colonised (eg Pseudomonas or B. Cepacia), median survival falls
What % UK CF patients are over 18?
50%
Why has median survival of CF increased?
CF centres MDT teams Physiotherapy Nutrition/Enzymes Antibiotics Aggressive approaches Annual flu/pnemococcal
Other than drugs, what can help improve quality of life?
Oxygen and NIV Exercise Support – physical, mental, social, financial, . Alternative therapies (massage, reflexology, exercise equipment, gym memberships) Advanced Care plans DNACPR discussions
