Cystic Fibrosis Flashcards
What is cystic fibrosis (CF)?
A genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidney, and other organs
What is the inheritance of CF?
Autosomal recessive
How does CF compare to other life-limiting autosomal recessive conditions in caucasians?
It is the most common
What is the incidence of CF?
1 in 2500 live births
What is the carrier rate of CF?
1 in 25
What is the fundamental problem in CF?
A defective protein called the CF transmembrane conductance regulator (CFTR)
What is the CFTR?
c-AMP dependent chloride channel found in the membrane of cells
What effect does the defective CFTR have?
Abnormal transport of ions across epithelial cells
How does CF affect the respiratory system?
Reduced fluid in airway surfactant, leading to reduced ciliary function and retention of mucus secretions
What can retention of mucus in the lungs result in?
Chronic endobronchial infections with specific organisms e.g. Pseudomonas aeruginosa
How can CF affect the immune system?
Leads to dysregulation of inflammation and defence against infection
How does CF affect the intestine of infants?
Thick, viscous meconium is produced leading to meconium ileus
What percentage of babies born with CF are affected by meconium ileus?
10-20%
How can CF affect the pancreas?
Block it due to thickened secretions
What does pancreatic obstruction lead to?
Pancreatic enzyme deficiency and malabsorption
What percentage of children with CF are affected by pancreatic exocrine insufficiency?
90%
How does CF affect the sweat glands?
Creates sweat with excessive levels of sodium and chloride ions
On what chromosome is the CFTR gene located?
7
How many gene mutations have been show to cause distinct defects in the CFTR?
Over 900
What is the most frequent gene mutation in CF in the UK?
F508
How does the genotype affect the phenotype?
Some are associated with milder disease and pancreatic sufficiency
How has genotype began to affect treatment options?
Has allowed for CFTR potentiators such as Ivacaftor and correctors such as Lumicaftor
What are CFTR potentiators useful for?
Restoring the function of CFTR in class III and IV mutations
What are CFTR correctors useful for?
Potentially restoring CFTR numbers in class II defects
What is the main risk factor for CF?
Caucasian ethnicity
What are the symptoms of CF?
- Recurrent chest infections
- Faltering growth
- Persistent wet cough producing purulent sputum
- Steatorrhoea
What causes the steatorrhoea and faltering growth?
Malabsorption due to pancreatic exocrine insufficiency
What are the signs of CF on examination?
- Hyperinflation of the chest
- Coarse inspiratory crepitations
- Expiratory wheeze
- Finger clubbing in advanced disease
How is CF often detected?
On newborn screening
Who is screened for CF?
All newborns
What does screening for CF help to reduce?
Delayed presentation with faltering growth and chronic chest infections
What is the initial screening test used to diagnose CF?
Heel prick test
What is looked for in the heel prick test for CF?
Immunoreactive Trypsinogen (IRT)
What happens to patients who are found to be IRT positive?
They are screened for common gene mutations
What happens to patients with at least 2 gene mutations associated with CF?
They undergo a sweat test to confirm the diagnosis
How is the sweat test performed?
Apply low-voltage current to pilocarpine applied to the skin, with sweat collected into capillary tube or absorbed onto a piece of filter paper
What constitutes a positive sweat test?
Cl in sweat is between 60-125mmol/L
How can pancreatic insufficiency be diagnosed?
Low faecal elastase
What are some differentials for CF?
- Asthma
- Other causes of failure to thrive
- Bronchiectasis
- Coeliac disease
- Primary ciliary dyskinesia
What are the 3 key points in the day-to-day management of CF?
- Infection control
- Physiotherapy
- Nutritional management
What are the main aims of these combined treatment strategies?
To ensure infants and children with CF do not have respiratory symptoms or symptoms of malnutrition
What do many CF specialists recommend in order to reduce the risk of respiratory tract infection patients with CF?
Prophylactic antibiotic treatment
What is usually recommended for prophylactic antibiotic treatment in patients with CF?
Flucloxacillin
What is recommended if there is an increase in respiratory symptoms or decline in lung function?
Rescue antibiotics
What is an indicator in CF for IV antibiotics?
Persisting signs or symptoms despite oral antibiotics
Why is vigorous IV antibiotic therapy often required?
In order to prevent lung damage
For how long are IV antibiotics given in more severe CF related infections?
14 days
How are IV antibiotics usually administered in CF?
Via a PIC line
What type of infection is more commonly associated with rapid decline in lung function?
Pseudomonas infection
What is used to treat pseudomonas infection?
Specific anti- pseudomonal antibiotics
What do more severe cases of CF often require?
Regular IV antibiotic therapy
How can regular IV antibiotic therapy best be administered?
Via a central venous catheter with a SC access port
What is the problem with using a central venous catheter with a SC access port?
They require monthly flushing and complications may develop
When and how often should children with CF begin engaging with physiotherapy techniques?
From diagnosis at least twice a day
What is the aim of physiotherapy techniques in CF?
To clear the airways of secretions
What physiotherapy techniques are advised for young children?
Chest percussion and postural drainage performed by parents
What physiotherapy techniques are advised for older children?
Controlled deep breathing exercises
What else may be useful in the physiotherapy management of CF?
Physiotherapy devices
What else is encouraged in CF?
Exercise
What should be assessed regularly in CF patients?
Dietary status
How is pancreatic insufficiency treated?
Oral enteric-coated pancreatic replacement therapy
When should pancreatic replacement therapy be taken?
With every meal and snacks
How is the dose of pancreatic replacement therapy determined?
Based on clinical response
What is essential in a CF diet?
High calories
How high must the calorie count be in a CF diet?
Around 150% of normal
How may a high calorie diet be achieved?
Over night feeding via gastrostomy
What else may CF patients require to supplement their diet?
Fat soluble vitamin tablets
What is the only therapeutic treatment that can be considered in end stage CF lung disease?
Bilateral sequential lung transplant
What is the current 10 year survival rate post Bilateral sequential lung transplant?
50%
What must be considered before deciding to perform a lung transplant?
- Co-morbidities
- Microbiology
- Psychological preparation
- Optimal timing
- Post-transplant care
How has the average life-expectancy of a CF patient improved?
From a few years to mid 30’s
What is the current predicted life expectancy of a baby born with CF?
Into the 40’s
What do 95% of CF patients ultimately die of?
Respiratory failure
What are the other common complications of CF?
- Meconium ileus
- Distal intestinal obstruction syndrome (DIOS)
- Infection
- Liver disease
- Respiratory complications
- Infertility
- Psychological impact
How many infants with CF are affected by meconium ileus?
10-20%
What does meconium ileus cause?
Intestinal obstruction
What are the typical symptoms of meconium ileus?
- Vomiting
- Abdominal distension
- Failure to pass meconium
What is usually needed to treat meconium ileus?
Surgical treatment
What can sometimes be useful in relieving the obsstuction caused by meonium ileus?
Gastrografin enema
What is a DIOS?
It is the later equivalent of a meconium ileus by where the mucofaeculent material obstructs the bowel
How is DIOS treated?
Combination of oral laxatives
What can chronic infection in CF lead to?
- Damage to bronchial wall
- Bronchiectasis
- Abscess formation
What organisms often cause infection in CF?
- Staph aureus
- Haemophilus influenzae
- Pseudomonas aeruginosa
- Burkholderia
Which organisms tend to cause rapid decline of lung function in CF?
Pseudomonas and Burkholderia
What are patients often advised to do as a result of high risk infection with specific organisms?
Avoid socialising with other CF patients
How many adolescent CF patients will have evidence of liver disease?
1/3
What evidence can be seen suggesting liver disease?
- Hepatomegaly
- Abnormal LFTs
- Abnormal USS
What may be beneficial to improve bile flow in patients with liver disease in CF?
Ursodeoxycholic acid
What does CF associated liver disease rarely progress to?
- Cirrhosis
- Portal hypertension
- Liver failure
What treatment is generally very successful in CF patients with severe liver disease?
Transplant
What respiratory complications becoming increasingly more likely as CF progresses?
- Chest infections
- Pneumothorax
- Life-threatening haemoptysis
Which gender are affected by infertility in CF?
Male
Why do males almost always experience infertility in CF?
They do not have a vas deferens
How may males with CF father children?
Through intracytoplasmic sperm injection
Are females affected by infertility in CF?
No, they tolerate pregnancy well unless they have severe lung disease
Why do patients with CF require psychological support?
They have to cope with a chronic and ultimately life-limiting disease
Which age group require particularly special psychological consideration?
Adolescents
