Cystic Fibrosis Flashcards
Is CF autosomal recessive or dominant?
Autosomal recessive
What is a recessive disease?
Occurs when you inherit 2 mutated genes, one form each parent
Healthy allele compensates effect of mutant allele
Homozygous state
What is the percentage of respiratory death being cause of death in CF?
90%
What is the most common autosomal recessive disorder in Caucasians?
Cystic Fibrosis
If both parents are carriers of CF mutant allele then what is the chance of inheritance?
1 in 4 chance will be infected
2 in 4 chance if carrier
1 in 4 of unaffected
What mutation is CF due to?
Mutation in the transmembrane conductance regulator protein (CFTR) which is coded on the 7th chromosome
What chromosome if the CFTR protein coded on?
Chromosome 7
What does the mutation in CFTR cause?
Abnormal function of the protein channel so chloride is trapped in the cell.
Sodium and water follow chloride and flow into cell
What are the consequences of abnormal function of protein channel?
Dehydrates airway surface liquid and mucous layer
Tick mucous sticks to mucous layer and causes shearing
Difficult to cough up
Mucous collects bacteria so there is a reduced ability to fight infection
How many mutation classes of CFTR are there?
6 classes
What is the commonest mutation of CFTR?
deltaF508 which is a class 2 mutation
What does 1 - 3 mutation classes give?
Severe disease as no functioning protein
What does 4 - 6 mutation classes give?
Milder disease as some functioning protein
What is antenatal testing?
This is before birth following indication of CF parent or sibling
What are the types of antenatal testing for CF?
Pre-implantation genetic diagnosis
Chorionic villous sampling
Amniocentesis
What is neonatal screening?
Just after birth
What is the neonatal screening used to diagnose CF?
Guthrie test - new-born bloodspot on day 5
If screen positive refer for assessment and sweat test
When does sweat tests happen?
Postnatally at any time
Explain sweat testing
Measures the conc. of chloride excreted in sweat. Chloride conc. is elevated in CF patients
Less reliable in adults and infants under 6 months old
What is an abnormal sweat chloride conc.?
> 60 millimoles per litre
High chance of CF
What is another postnatal test for CF that is not sweat testing?
faecal elastase
What are the 3 possible outcomes for prenatal, antenatal and postnatal testing?
CF, Not CF or CF - screen positive inconclusive diagnosis (SPID)
What part of the body does CF affect?
Can affect any part of the body as a multi-system disease
Where are the main conditions of CF?
Pancreatic insufficiency
Diabetes
Infection and bronchiectasis
Explain pancreatic insufficiency
CFTR affects pancreas
Pancreas produces enzymes that digest food but there is a lack of these enzymes (trypsin and colistin)
What does a lack of the enzymes trypsin and colistin cause?
Malabsorption
Abnormal stools - pale, offensive and float
Failure to thrive so Importance of growth records and growth charts
What does class 1-6 have on level of pancreatic insufficiency?
Class 1-3 are pancreatic insufficient
Class 4-6 have some pancreatic function
How much CFTR function do you need for sufficient pancreatic function?
5% CFTR function
Can be asymptomatic
What can result from recurrent chest infections?
Pneumonia
Bronchiectasis
Scarring
Abscesses
What does abnormal electrolyte transport across the membrane cause?
Dehydration of airway surface layer - mucus cant easily slide up and be coughed up
This decreases muco-ciliary clearance
What happens when there is decreased muco-ciliary clearance?
Mucous sticks to mucosal surface and causes shearing and inflammation
Increases access to bacteria and decreases killing of bacteria
Explain the cycle of events that cause repeated resp. infections?
Decreased muco-ciliary clearance and killing of bacteria and increase in bacteria adherence -
Bacterial colonisation -
Inflammation, Mucus plugging, airway ulceration and damage -
Bronchiectasis - repeat
Explain bronchiectasis
Airways become thickened, dilated and stiff - retain mucous which becomes infected and impairs O2 exchange
What happens to respiratory of patient with CF?
Progressive respiratory decline occurs
Progressive airway obstruction and can lead to respiratory failure
What is the clinical sign of progressive bronchiectasis?
Chronic sputum production - cupfulls
What does a CT scan show in a patient with CF?
Tramlines
Signet rings
Mucous plugging
Consolidation - infection
What is a clinical presentation of CF?
Clubbing as result of low O2
Who is involved in the treatment of CF?
CF is a multiorgan disease and needs MDT to improve long term outcome - shared care is essential
What is the treatment for pancreatic insufficiency in CF?
Aim is to boost nutrition
1. Replace enzymes - Creon
2. Diet - high energy and calorie with supplement drinks
3. Nutritional supplements - fat soluble vitamins and minerals
Explain treatment of mucus obstruction and inflammation
Airway clearance via physiotherapy, mucolytics and bronchodilators
What is the treatment for infection in a patient with CF?
Antibiotics - oral, IV or nebulised
What is the treatment for increased inflammation?
Azithromycin - can be used as main term treatment if at lose dose
What is the treatment for fibrosis/ scarring/ bronchiectasis?
Supportive treatment and management of symptoms are irreversible
Explain diabetes and CF
Type of diabetes and management differs from non CF patient
Need joint Diabetic/ CF clinics and CF dietician is vital
What is the commonest type of diabetes seen in CF?
Not enough insulin from the pancreas or insulin is not working properly
Explain osteoporosis in CF patients
Bone mineral density falls in patients with CF - slower gain and faster loss.
Increased risk of fractures and can exclude lung transplant
What are some predictors of low BMD?
Low FEV1, frequent antibiotic courses, steroids, malnutrition, low exercise, age, male, diabetes, vit D deficiency and delayed puberty
Explain pneumothorax and CF
Affects 3-4% of CF patients in their lifetime
Treatment is same as other patients which is insertion of chest drains or using aspiration to reflate lung
What causes haemoptysis in patients with CF?
Bronchial wall destruction causing coughing of blood
What is treatment for minor and massive haemoptysis?
Minor - blood streaking so no
specific treatment
Massive - Admit and resuscitate, may need bronchial angiogram and embolization
What is the drug burden on CF patients?
High drug burden
Can be around 37 drugs and Creon alone is like 30-40 tablets a day
What are the bacteria that is a contraindication to lung transplant?
Burkholderia Cenocepacia
as poor survival
M. Abcessus as highly resistant and grows rapidly
What does the new modulator drugs target?
Addresses different parts of CFTR production, processing, folding, transport and insertion into membrane
What does Kaftrio modulator drug do?
Small benefits in lung function
Main benefits are fall in chest exacerbations, rise in weight and improved QoL
What are the new modulator drugs?
Kalydeco
Orkambi
Symkevi
Kaftrio
What are indications for lung transplantation?
Rapidly deteriorating lung function
FEV1 < 30% predicted
Life threatening exacerbations
If estimated survival is less than 2 years
Recurrent pneumothorax and severe haemoptysis
What are some absolute contra-indications to transplant?
Other organ failure, malignancy within 5 years, significant peripheral vascular disease, drug nicotine or alcohol dependency, active systemic infection or microbiological issues
What are some relative contra-indications where clinical judgement is needed?
Other organ dysfunction, non-compliance, high dose of steroids, osteoporosis, low or high BMI, previous thoracic surgery and psychological
Why has survival median for patients with CF got better?
CF centres, MDT, Physiotherapy, nutrition/enzymes, abx, aggressive approaches and annual flu/ pneumococcal
What are other things to consider which can improve QoL?
Oxygen and NIV at home
Exercise
Support
Advanced care plans and DNAR discussions
