Cystic Fibrosis
aka CF
NBS misses ?percent
Spectrum of disease (Classes)
No function
- Class I mutation: defective protein production
- Class II mutation: defective protein processing into the cell membrane (dF508)
- Class III mutation: defective opening to ATP
Reduced function
- Class IV mutation: defective conduction
- Class V mutation: reduced amounts of functional protein
- Class VI mutation: reduced stability
Pathology
Mean survival 45yo
Lung function ultimately determined by nutrition
Staph creates biofilm in lungs, leaving vulnerable to pseudomonas
Presentation (Respiratory Hx, Gastrointestinal Hx)
Chest infections (cough, sputum, haemoptysis)
Lethargy
Anorexia
Ex (Resp Ex
FTT
- reduced subcutaneous tissue
- thigh/buttock wasting
- ht/wt
Clubbing
hyponatraemia/hypoK
diarrhoea and rectal prolapse (pancreas insuf > fat malabsorption)
Ix
Sputum culture/BAL
CXR
PFTs
Overnight oximetry
Faecal elastase (not affected by Creon)
LFTs
Abdo US/CT/Tn99m Scint
Endoscopy - upper / lower
Liver Transplant
Rx
150% RDI with aim of BMI >50% (need to supplement +/- PEG if not meeting)
- 40% fat with Creon
Exercise
Hydration (dehydration increased risk of infection and DIOS)
Airway clearance
Physio
Mucolytic
- Dornase alpha (Pulmozyme)
- Hypertonic saline 7%
Bronchodilators
Port
Antistaph prophylaxis
Pseudomonas eradication
Anti-Inflammatory macrolides (azithromycin)
Infection control to prevent transmission
Lung transplant
Immunisations: influenza and pneumococcal
Enzyme replacement (Creon)
Vitamins
Salt tablets
Gene therapy
Orkambi (combined lumacaftor + ivacaftor) CFTR corrector and potentiator for homozygous dF508
Recurrent chest infections
Allergic bronchopulmonary aspergillosis (ABPA) (seen in Asthma or CF)
Pubertal delay
adverse effects of medications including drug allergies
complications of venous access: recurrent thrombus
mental health issues
musculoskeletal disorders
NBS misses ?percent
- Screens immunoreactive trypsin (a pancreatic enzyme precursor)
- High get ?gene screen ?sweat test
- ~1:25 carrier in Australia, = 1:2500 births = 3000 Australians
- caused by mutations in long arm of chromosome 7 (7q31.2)
- dF508 = 70% of australasia disease, deletion of 508th DNA triplet)
- single amino acid loss (i.e. 3 nucleotides, no frame shift, rest of protein (AAs) intact
- dF508 = 70% of australasia disease, deletion of 508th DNA triplet)
- leads to abnormal functioning of cystic fibrosis transmembrane conductance regulator (CFTR) protein, a cyclic-AMP-regulated chloride (and bicarbonate) channel on the apical surface of epithelial cells
Spectrum of disease (Classes)
No function
- Class I mutation: defective protein production
- Class II mutation: defective protein processing into the cell membrane (dF508)
- Class III mutation: defective opening to ATP
Reduced function
- Class IV mutation: defective conduction
- Class V mutation: reduced amounts of functional protein
- Class VI mutation: reduced stability
Pathology
- increased sweat chloride
- reduced mucous chloride = thick = impaired mucociliary clearance = chronic infection
Mean survival 45yo
Lung function ultimately determined by nutrition
Staph creates biofilm in lungs, leaving vulnerable to pseudomonas
Presentation (Respiratory Hx, Gastrointestinal Hx)
Chest infections (cough, sputum, haemoptysis)
Lethargy
Anorexia
Ex (Resp Ex
FTT
- reduced subcutaneous tissue
- thigh/buttock wasting
- ht/wt
Clubbing
hyponatraemia/hypoK
diarrhoea and rectal prolapse (pancreas insuf > fat malabsorption)
Ix
Sputum culture/BAL
CXR
PFTs
Overnight oximetry
Faecal elastase (not affected by Creon)
LFTs
Abdo US/CT/Tn99m Scint
Endoscopy - upper / lower
Liver Transplant
Rx
150% RDI with aim of BMI >50% (need to supplement +/- PEG if not meeting)
- 40% fat with Creon
Exercise
Hydration (dehydration increased risk of infection and DIOS)
Airway clearance
Physio
Mucolytic
- Dornase alpha (Pulmozyme)
- Hypertonic saline 7%
Bronchodilators
Port
Antistaph prophylaxis
Pseudomonas eradication
Anti-Inflammatory macrolides (azithromycin)
Infection control to prevent transmission
Lung transplant
Immunisations: influenza and pneumococcal
Enzyme replacement (Creon)
Vitamins
Salt tablets
Gene therapy
Orkambi (combined lumacaftor + ivacaftor) CFTR corrector and potentiator for homozygous dF508
Recurrent chest infections
- Staph and Hinf pre pseusdomonas
- E. coli, Streptococcus pneumonia, Burkholderia cepacia complex, Achromobacter xylosoxidans, Stenotrophomonas maltophilia, Klebsiella, Enterobacter, non-tuberculous mycobacteria, fungal species.
- Post pseudomonas
- Macrolides provide anti-inflammatory improvement once pseudomonas established
Allergic bronchopulmonary aspergillosis (ABPA) (seen in Asthma or CF)
- wheezing, decreased exercise tolerance, rust coloured sputum, and reduced lung function +/- haemoptysis
- Dx (Asthma or CF) + (Aspirgillus skin test or IgE positive) + High IgE (>1000IU/ml) + 2 of (CXR/Eosin >500/ precipitating antibodies)
- Rx high-dose corticosteroids +/-
- Itraconazole (with specialist input) monitor serum concentrations to avoid toxicity / subtherapeutic doses.
- Glucose tolerance test
- Meconium ileus
- DIOS
- ?Short gut from resection post above ileus
- Rectal prolapse
- Pancreatic insufficiency > Fat malabsorption> FTT + nephrolithiasis
- CF liver disease, portal hypertension
- GORD
- Fibrosing colonopathy
- Gastrostomy
Pubertal delay
adverse effects of medications including drug allergies
complications of venous access: recurrent thrombus
mental health issues
musculoskeletal disorders