Cystic Fibrosis in Adults Flashcards
How common is cystic fibrosis?
- Most common autosomal recessive disorder in caucasians
- 1 in 2000/2500 caucasian live births
- 1 in 25 carriage rate
- Respiratory failure is the cause of death in 90% of people with CF
Why has the survival for CF improved?
- CF centres
- MDT teams
- Physio
- Nutrition/enzymes
- Antibiotics
- Aggressive approaches
- Annual flu/pneumococcal
What is the Cystic Fibrosis protein?
Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and chloride channel in vertebrates that is encoded by the CFTR gene.
What occurs due to the mutation of the CFTR gene?
Abnormal transport of chloride and sodium across epithelium
- Reduced chloride secretion from epithelium
- Reduced Na absorption from lumen
= thick secretions
= Impaired bacterial killing via neutrophils as normal chloride required
What is the advantage in mice being heterozygous for the CFTR gene?
Increased resistance to salmonella, cholera toxin
What are the 5 classes of disease: pancreatic insufficiency?
Class 1: no synthesis G542X
Class 2: Increased degradation DF508
Class 3: Defective reg G551Db
Class 4: Abnormal conduction R117H
Class 5: Reduced synthesis/trafficking A455E
What are challenges for patients in CF for adults?
- Transition is a major challenge, new MDT team
- Prognosis
- Promise of new drugs
- Possibility of lung transplant
- Other conditions: diabetes, liver disease, osteoporosis, fertility issues, haemoptysis etc
What are commonest presentations of CF in newborns?
- Meconium Ileus (15%)
- Prolonged conj jaundice
- Newborn screening
- Screening due to FH
What are commonest presentations of CF in infancy and children?
- FTT (29%)
- Abnormal stools (24%)
- Recurrent LRTI/symptoms (40%)
- Rectal prolapse 20%
- Nasal polyps (10-40%)
What are commonest presentations of CF in adults?
- Infertility (esp in men)
- Bronchiectasis
- Clubbing
- Mild resp symptoms/recurrent LRTI (40%)
- Hyperinflation
Why does pulmonary infection occur in CF?
CFTR abnormality
- Decreased mucociliary clearance
- Increased bacterial adherence
- Decreased endocytosis of bacteria
Features of progressive airflow obstruction
- Survival related to FEV1
- Increasing exertional dyspnoea
- Brochodilators (inhaled nebulised)
Features of respiratory failure
Type 1 = decreased PaO2
Type 2 = Decreased PaO2, Increased PaCO2
Oxygen, ambulatory oxygen
Nocturnal NIV, symptomtic relief, bridge to LTx
What does a cystic fibrosus CT scan usually show?
- Tramlines
- Signet rings
- Mucous plugging
- Consolidation
Features of Type 2 Diabetes Mellitus in CF
- Often preceded for years by falling lung function, BMI
- Almost never get DKA, type 1 DM only rarely seen
- Complication risk same as non CF pts but pulmonary disease gets there first
CF issues in type 2 diabetes mellitus
- Compliance with diet a problem
- Low sugar/high fibre diet not appropriate
- OGTT/HBA1C used but not perfect
- Insulin of benefit, not so much oral hypoglycaemics
Features of Osteoporosis in CF
- Significant BMD (bone mineral density) decrease in 1/3 adults patients with CF
- Slower gain, faster loss, worse the sicker you are
- May exclude lung transplant
What does osteoporosis in CF occur due to?
- Malnutrition and low BMI
- Steroids
- Delayed puberty and hypogonadism
- Inflam cytokines from sepsis (we know BMD falls in septic pts)
- Vitamin D/K deficiency
- Lung Tx/drugs
What are predictors of low BMD (bone mineral density)?
- Low FEV1
- Frequent a/b courses
- Steroids
- Low BMI
- Low exercise
- Age
- Male
- Diabetes
- Vit D
- Delayed puberty
Features of Pneumothorax in CF
- 3-4% Cf patients during lifetime
- Especially if older, more severe obstructive lung disease
- 16-20% > 18
- Males=Females
Treatment same as other patients = drain, pleurodesis, surgery
Features of Haemoptysis in CF
- Bronchial wall destruction
- Minor (60%) = blood streaking common, no special treatment
- Massive in 1% patients each year, may need embolisation
Risk factors of Haemoptysis
- Severity
- Exacerbations
- Fungal
- Liver disease
- Vitamin K deficiency
Microbiology: features of Pseudomonas Aeroginosa
- Colonisation increases with age
- Acquired from enviroment, other CF patients, segregation and disinfection policies
Colonisation associated with: reduced life expectancy, rapid decline in lung function
First isolation: attempt eradication - 3 months of treatment
Microbiology: features of Burkholderia Cepacia
- Environmental organism (causes onion rot)
- Acquired from: environment, other CF patients (epidemic strains more virulent), segregation policies
- Colonisation associated with: reduced life expectancy 16 vs 39 years, rapid decline in lung function, do worse in pregnancy
- Innate resistance to most antibiotics
- Genomovar III contraindication for transplantations
Features of Sternotrophonas Maltophilia
- Increasing frequent colonisation
- Usually after pseudomonas, but can occur as first Gram negative infection
- Multiple antibiotic resistance
- Unsure if detrimental to prognosis
Features of Aspergillus
- Comes from environment, not person to person
- Can cause spectrum disease
- E.g. coloniser, infection, allergy
Features of Non TB Mycobacteria in CF (NTM)
Isolated in up to 13% CF patients
- MAI = 75% of these
- M. abcessus grows rapidly, comprises 16% of NTM patients with CF
May not need treatment:
- Treat if clinical/lung function/CXR deterioration
Features of Mycobacterium Abscessus
- Currently rapid increase in number of isolates
- Highly resistant
- Contraindication for transplantation
- Eradication: 1 month in hospital then maintenance treatment for 1 year- side effects, failure
Treatment for pulmonary infection
- Treat early and aggressively with antibiotics
- Oral antibiotics (e.g. Staph, Haemophilus, Pneumococcus)
- IV antibiotics (e.g. PA, Stenotrophomonas, Burkholderia)
- Two antibiotics, liaise with microbiology
- If multiply resistant, test for synergy between antibiotics
- Large doses (include volume distribution, increased clearance)
- Two week courses
- Indwelling suncutaneous ports (vascuports)
Is there evidence for antibiotics in acute exacerbations?
- Not much evidence for regular ivs but anecdotally seem to work in some patients
- Concerns re-resistance
Antibiotics: Can resistance it vitro still work in combination in vivo?
Yes it may still work
- CF organisms often grow poorly on standard media
- Rise in FEV1 in iv tobra/ceftaz trial not related to whether ps was sensitive to a/b or not
- Never use 1 iv: avoids resistance.
Some evidence that 2 a/b use reduces readmiss rates
- Synergy testing may help
Features of Nebulised or Inhaled antibiotics
- Not used instead of intravenous antibiotics
- Colobreathe inhaler or ocassionally colomycin nebuliser
- TOBI inhaler or occasionally Tobramycin nebuliser: it treats Pseudomonas aeruginosa
Why would bronchodilators be used in CF?
CF patients may have airway obstruction due to:
- Asthma/Atopy: BHR in 40% CF patients
- Mechanical: bronchial plugging, inflammation > bronchial wall thickening
- Many patients (especially milder disease): increase in FEV1 despite absence typical asthma symptoms
Features of airway clearance: Chest Physio
- Autogenic drainage, active cycle of breathing, huffing
- Airway oscillating devices (PEP device), percussion vests
- All patients with sputum should do physio: compliance issues
- Expensive devices not routinely recommended as lack of data
Features of Mucolytics
- Reduce viscosity of phlegm
- Making it easier to expectorate
Examples of Mucolytics
- Pulmozyme
- Hypertonic saline
- Carbocysteine
- Bronchitol
What is the suggested regime to optimise drug delivery?
- Bronchodilator MDI
- Hypertonic saline
- Chest physio
- DNAse
- (Neb antibiotics)
Features of anti-inflammatory therapy: Azithromycin
- Antibacterial and anti-inflammatory effects
- Reduces biofilms
- Increased lung function, decreased decline, decreased exacerbation rate by 40%
What are new drugs - Potentiators and Correctors in CF?
- Ivacaftor
- Ivacaftor/Lumacaftor (Orkambi)
- Tezacaftor/Ivacaftor (Syndeco)
- Triple therapies in development
Small benefit in lung function.
More significant benefit is fall in pulmonary exacerbations and weight gain
What are indications for a double lung transplant?
- Rapidly deteriorating lung function
- FEV1 <30% predicted
- Life threatening exacerbations
- Estimated survival <2 years
Survival features for a double lung transplant
- 70-80% at 5 years
- 50% at 10 years
- Gradual attrition due to bronchiolitis obliterans
- Viewed as a measure to prolong survival and improve quality of life
What are other things to consider to improve quality of life?
- Oxygen and NIV
- Exercise
- Support
- Advanced care planning
- DNAR
