Cystic Fibrosis 1 Flashcards
What is the most common life shortening inherited disease in Northern Europeans?
Cystic fibrosis
What kind of inheritance does CF show?
Autosomal recessive
What is the gene prevalence of CF?
1:25
What is the disease prevalence of CF?
1:2500
Where does the CF gene lie?
Long arm of chromosome 7
What is the CF gene?
Cystic fibrosis transmembrane conductance regulator (CFTR)
How many known mutations are there of the CF gene?
>2000
How many mutations of the CF gene are CF disease associated?
About 30
What can different mutations result in?
Different phenotypes of the disease
How many classes of mutations are there?
6
What is the most common CF gene mutation?
phe508del ((DF508)
What is the class of mutation 1?
No synthesis
What is the class of mutation 2?
Block in processing
What is the class of mutation 3?
Block in regulation
What is the class of mutation 4?
Altered conductance
What is the class of mutation 5?
Reduced synthesis
What is the function of the cystic fibrosis transmembrane regulator (CFTR) gene?
Cilial collapse (regulates lipid volume on epithelial surface by reducing chloride and increasing sodium)
What does a mutation of the CFTR gene cause?
Excessive, innate inflammation
Thick, sticky mucus
What does collapsed cilia cause?
Traps organisms
What are the presenting features of CF?
Recurrent chest infection
Failure to thrive in children
Nasal polyps and sinusitis
Male infertility
What neonatal screening is done for CF?
New-born bloodspot day 5 (Guthrie test)
What is the test called for screening CF?
Guthrie test
What happens if the Guthrie test is positive?
Refered for clinical assessment and sweat test
What is required to make the diagnosis of CF?
Clinical assessment
Sweat test
Repeat CF mutation analysis
What are the possible diagnostic outcomes?
CF
Not CF
CF screen postive inconclusive diagnosis
Why could a screen positive still be an inconclusive diagnosis?
Dependant on sweat test (normal)
What is done following the identification of a CF patient who is going to become a parent?
Antenatal screening
What antenatal screening is done for CF?
Pre-implantation genetic diagnosis
Chorionic villus sampling
Amniocentesis
What does the management of CF involve?
Multi-organ disease
Specialist multi-disciplinary team
Share care with local clinics
Primary care
What role does primary care have for CF?
Surveillance
Early treatment of infection
What are cardinal features?
Major clinical symptoms
What are major clinical symptoms called?
Cardinal features
What are the 2 cardinal features of CF?
Pancreatic insufficiency (85-90%)
Recurrent bronchopulmonary infection
What does pancreatic insuficiency cause?
Abnormal stools (pale or orange, very offensive and greasy)
Failure to thrive
What are some consequences of recurrent bronchopulmonary infections?
Pneumonitis
Bronchiectasis
Scarring
Abscesses
What does the treatment of pancreatic insuficiency involve?
Enteric coated enzyme pellets
High energy diet
Fat-soluble vitamin and mineral supplements
What is the cycle of CF lung disease?
1) Mucus obstruction inflammation
2) Infection
3) Increased inflammation
4) Fibrosis/scarring/bronchiectasis
What is mucus obstruction helped by?
Airway clearance physiotherapy
What is infection helped by?
Antibiotics
What is inflammation helped by?
Azithromycin
What are common organisms in infections with CF?
Staph aureus and haemophilus influenza in early years
Pseudonomas aeruginosa in later years
What are less common organisms with infections with CF?
Burkholderia cepacia
Stenotrophomonas maltophilia
MRSA
Atypical mycobacterium
Lung microbiome
What can be done to try and prevent infections?
Eradication of early infections
Reduce inflammation
Suppress bacterial load of chronic infections
Annual influenza vaccine
Mucolytics
Airway clearance
Prophylactic against staph aureus
What is mucolytics?
Medicine that makes mucus less thick
What is medicine that makes mucus less thick called?
Mucolytics
What medicines reduce inflammation?
Ibuprofen
Azithromycin
Prednisolone
What treatment is currently being trialed?
CFTR modulator treatment which allows us to edit the gene
What are some complications of CF?
Dysmotility
Hepatopathy
Upper airway popyps and sinusitis
Osteopenia
Arathropathy
Heat exhaustion
Bilateral absence of vas deferens
Vaginal candidiasis
What social and economical impacts does CF have on the patient and their family?
Barriers to making friends as seen as different (drugs, missing school, cough, different diet)
Increased depression/anxiety
Low adherence to time consuming treatments
Siblings
Increased cost to family (time of work, financial benefits)
What are the cornerstones of CF treatment?
Proactive treatment of airway infection
Good nutrition
Active lifestyle
How has the prognosis for CF changed in the last few decades?
Massively improved
