What is the gene prevalence of cystic fibrosis in Europe?
1:25
What is the disease prevalence of cystic fibrosis in Europe?
(1:25 x 1:25) x 4 = 1:2500 will have CF
Describe the inheritance of CF
Autosomal recessive
Describe the mutation associated with CF
Autosomal recessive mutation on q arm of chromosome 7 for the CF transmembrane conductance regulator (CFTR)
What is the most common deletion associate with CF
phe508del - codon deletion leads to improper folding of protein and it can not leave the ER to be presented on the surface and is instead recognised as faulty and destroyed
Seen in 70% of Northern European CF patients
How does CF affect the CFTR?
Can affect function or the levels of surface expression of the CFTR
What is the function of CFTR?
Active transport for chloride out into the mucus, regulating the liquid volume on epithelial surfaces/in the mucus
In CF, there is reduced Cl efflux and increased Na influx, leading to the development of thick mucus, hard to cough up
Describe neonatal screening for CF
Guthrie heel prick - day 5, CF and PKU
Immunoreactive trypsinogen levels in blood
Mutation analysis
Sweat test - Cl >60= positive for CF
What are the 2 cardinal features of cystic fibrosis?
Pancreatic insufficiency - abnormal stools, failure to thrive
Recurrent bronchopulmonary infections
How do you treat pancreatic insufficiency in CF?
Enteric coated enzyme pellets High energy diet - lots of fats Fat soluble vitamins and minerals H2 antagonist inhibitors Proton pump inhibitors
What are some complications of recurrent bronchopulmonary infections?
Pneumonitis Bronchiectasis Haemoptysis Scarring Abscesses Respiratory failure
How do you prevent infections in CF?
Segregation Airway clearance and adjuncts Mucolytics Prophylactic antibodies e.g. Staph Aureus Annual influenza jabs
How do you treat chronic infections in CF?
Continue Abx
Try and reduce bacterial load
Treat exacerbations
Reduce inflammation - ibuprofen, prednisalone and azithromycin
What is the predicted average life span of CF patients in the 21st century?
> 50yo
What are some other manifestations of CF that can lead to its identification?
GI dysmotility Hepatopathy Upper airway polyps and sinusitis Diabetes Osteopenia Heat exhaustion Bilateral absence of vas deferent Male infertility Vaginal candidiasis and stress incontinence
List some airway clearance techniques
Percussion and drainage
Autogenic drainage
Active cycle of breathing
List some airway clearance adjuncts
Positive expiratory pressure mask
Cornet/flutter
High frequency chest wall oscillation
List some mucolytics
DNase alfadornase
Hypertonic saline
How does undiagnosed CF in adults usually present?
Recurrent pulmonary infections Pancreatic insufficiency GI problems DM Liver disease Osteoporosis Infertility
What do abnormalities in CFTR lead to?
Decreased mucociliary clearance, increased bacterial adherence and decreased endocytosis of bacteria = infections
List some important infectious agents in CF
Pseudomonas aeruginosa
Burkholderia cepacia
Stenotrophomonas maltophilia
Mycobacterium abscessus
Describe Pseudomonas aeruginosa infections in CF
Colonisation increases with age Forms a protective biofilm Rapidly acquired multi drug resistance Reduces life expectancy by 10 years Rapid decline in lung function
Why does colonisation of Pseudomonas aeruginosa increase with age?
Repeat antibiotic use
Environment
Exposure from other CF patients
How do you treat Pseudomonas aeruginosa infections?
Oral ciplofloxacin and nebulised colomycin
If fails:
IV Ceftazidine and nebulised colomycin
Describe Burkholderia cepacia infections and CF
Organism acquired from environment and other CF patients
Associated with reduced life expectancy of 20 years, rapid decline in lung function and some patients develop CEPACIA syndrome, causing rapid deterioration
Innate resistance to most antibiotics
What is Burkholderia cepacia Genomovar III a contraindication of?
Transplantation
Describe Stenotrophomonas maltophilia infection in CF
Increasing frequency of colonisations
Usually after Pseudomonas
MDR, unsure of effect on prognosis
Describe Mycobacterium abscessus infection in CF
Rapid increase in infections
Due to increased use of azithromycin?
Resistant to all anti-TB drugs
CI for transplantations due to abscesses
Which infections require oral antibiotics?
Staph
Haemophilus
Pneumococcus
Which infections require IV antibiotics?
Pseudomonas
Stenotrophomonas
Burkholderia
What antibiotic types are used?
beta lactam and aminoglycosides
What is Ivacaftor?
CFTR potentiator for G551D patients, improves the transport of Cl ions
When are CF patients indicated for lung transplantation?
Rapidly deteriorating lung function FEV1 <30% predicted Life threatening exacerbation Estimated survival <2 years Severe weight loss Hypoxia at rest Desaturations at night Hypercapnia Recurrent worsening sepsis Worsening QOL
What two infection types are contraindications for lung transplantation?
Burkholderia cepacia (Genemovor III) Mycobacterium abscessus
Describe fertility issues in CF patients
No effect on sexual function
Puberty may occur up to 2 years later
Fertility affected in men (blocked/absent vas deferens)
Females fertile but poor nutrition may affect conception
What is the outer shell of an ovum called?
Zona pellucida
What are some options available for men with fertility issues trying to conceive?
Adoption
Artificial insemination with donor sperm
Intra-cytoplasmic sperm injection
What are the possible outcomes of assessment for transplantation?
Active list Passive list Too well Decision not to go on list Too unwell
List some absolute contraindications for lung transplantation
Other organ failure Malignancy within 5 years Significant peripheral vascular disease Drug/nicotine/alcohol dependance (6m off) Active systemic infection Mycobacterial abscessus infections Burkholderia Cepacia Genomovor III
List some relative contraindications for lung transplantation
Organ dysfunction Non-compliance of treatment Steroids >20mg daily LT Absence of recognised social support Osteoporosis Low BMI (18+) Surgical risks e.g. previous thoracic surgery