Cystic Fibrosis and Bronchiectasis Flashcards
What is the approximate median life expectancy for homozygous F508-del cystic fibrosis?
UK median survival of 46 years for males and 41 years for females in homozygous F508-del cystic fibrosis sufferers
In adults who should we consider investigating for CF?
- Persistent isolation of Staph Aureus in sputum
- Feature of malabsorption
- Male primary infertility
- Upper lobe bronchiectasis (not lower lobe)
- History of childhood steatorrhoea
- Screening investigations should include two measurements of sweat chloride and CFTR genetic mutation analysis
How is CF diagnosed ?
Blood spot (babies) ; immunoreactive trypsin test
OR
Clinical manifestation supported by sweat or gene test
OR
Clinical manifestation alone in rare case of people with symptoms who have normal sweat or gene test
What are the complications of CF?
Being underweight
Meconium Ileus (affects between 1 in 7 new babies)
Fat soluble vitamin deficiencies (ADEK)
DIOS
Muscle pain and arthralgia
Male infertility (almost all males with CF are infertile)
Reduced female fertility
Upper airway complications
Chronic liver disease
Urinary stress incontinence
CF related diabetes
Reduced bone mineral density
(Less common - CF related arthritis , delayed puberty and renal calculi)
What are the mucoactive agents used in CF?
Dornase Alpha - first choice, if inadequate response with dornase alone can add in Hypertonic saline
If unable to use can think about mannitol
Outline Staph Aureus infection in CF
Give Flucloxacillin as prophylaxis from diagnosis to 3 years and consider upto 6
If test positive start treatment dose anti S.Aureus abx
NB this is MSSA ; if MRSA will need micro advice (don’t routinely use abx to suppress chronic MRSA in those with chronic pulmonary disease)
MRSA assoc with accelerated lung function decline and increase mortality
Outline approach to Pseudomonas Aeruginosa in CF patients
If clinically well: Oral or IV plus inhaled anti-pseud abx ; followed by extended oral + inhaled
If clinically unwell: IV plus inhaled anti pseud, followed by oral and inhaled
If CF pt on colistin nebs but still deteriorating due to Pseud , what can be trialled ?
Aztreonam
Nebulised Tobramycin
Tobramycin DPI
Outline DIOS
Distal Intestinal Obstruction Syndrome - 10% risk for CF patients , once had , more likely to recur (50%)
Suspect in those with CF who have acute onset of peri umbilical or RLQ abdo pain and :
- palpable mass in the RLQ
- faecal loading in the RLQ on plain x ray
- clinical fx of partial or complete intestinal obstruction such as vomiting
Ix: US or CT
Tx: IVF ; gastrograffin as first line treatment , if not effective can consider PEG solution orally ** surgery is last resort
To try to avoid DIOS optimise pancreatic enzyme replacement and regular Tx with stool softener
What should make you think of CF diabetes ?
Increased weight loss, reduced lung function, increased frequency of exacerbations, excess tiredness
What is Kaftrio?
Triple combination drug for CF
Contains:
- Ivacaftor
- Tezacaftor
- Elexacaftor
(ITE)
Need to be:
- Age over 3
- 2 copies of the F508 del mutation or one copy of the F508 del and any other mutation
(Approx 90% have mutation)
In trials , increase in FEV1
What is Symkevi?
Ivacaftor and Tezacaftor
(IT)
Need to be:
- Aged over 2
- Two copies of F508 del mutation
- One copy of F508 del and another residual function mutation
(Approx 55% CF population)
Increase in FEV1
What is Orkambi?
- Ivacaftor and Lumacaftor
(IL) - two copies of F508 del mutation
- slows decline in lung function
(Approx 50% have mutation)
What is Kalydeco?
Ivacaftor
Effective in anyone with one of nine gating mutations
(Improvement in lung function and reduction in sweat chloride levels)
Outline the genetics for CF
Autosomal Recessive condition - need 2 copies of the disease causing mutation
CFTR gene located on long arm of chromosome 7
90% of patients have ≥ 1 copy of F508del ; 48% are homozygous for F508 del
What is the carrier rate for CF in UK?
1 in 25
What is the live birth rate of CF in UK?
1 in 2500
How do you interpret sweat test results ?
<30 NORMAL
30-60 INTERMEDIATE
> 60 ABNORMAL
NB can have CF and have a normal sweat test but this is less than 1%
If intermediate result can do nasal potential difference
Genetic panel CF50 is first line
What is the dominant pathogen for CF patients in childhood ?
Staph Aureus
What is the dominant pathogen for CF patients in teens/adulthood ?
Pseudomonas
What is the Leeds Criteria ?
Chronic Pseudomonas Aeurginosa infection as >50% samples +ve in last 12 months
What are the issues with P.Aeurginosa colonisation in CF?
Associated with accelerated decline in lung function and increased frequency of exacerbation and incr frequency of exacerbation is a predictor of mortality (≥2 per year associated with reduced survival)
How do we eradicate P.Aeruginosa in CF?
3/52 - 3/12 or Cipro plus nebulised colomycin
Or
Nebulised Tobramycin for 1/12
Nebulised Aztreonam for 1/12
IV abx if unwell
NB all eradication regimens include nebulisation as you achieve higher concentration in the airway than with systemic abx
Do we treat chronic Pseud colonisation in CF?
YES! Unlike non-CF bronchiectasis where treat depending on exacerbation frequency in CF we treat them
Nebulused Colomycin or alternatively Nebulised Tobra alternate month or aztreinam alternate month
Outline Burkholda Cepacia
Causes accelerated decline in FEV1 and increase in mortality
Can get Cepacia syndrome which is fever , consolidation, sepsis , inflammation and death
very resistant and difficult to treat can be barrier to transplant
Outline M. abscessus in CF
Accelerated lung function decline, multi resistant to eradication and contraindication to lung transplant
Which drugs affect CFTR Function?
Ivacaftor
Which drugs affect CFTR quantity ?
Tezecaftor
Elexacaftor
Lumacaftor
Outline Haemoptysis as complication in CF
Mortality 5-16%
Haemoptysis - 4% will have massive ; more likely if older of FEV1 <40%
Bleeding from bronchial circulation in 90% (usually bronchial circulation only carries 1% of cardiac output but this increases in disease as chronic hypoxia and inflammation drives angiogenesis and bronchial hypertrophy)
Massive >100ml in day or 250mls one go
if mild : continue physio and dornase but stop hypertonic and mannitol
If severe stop everything ; TXA; broad spectrum abx ; bleeding side down; terli ; BRONCHIAL ARTERY EMBOLISATION - gold standard
What are the risks of bronchial artery embolisation?
Chest pain
Inflammation and exacerbation
Pulmonary infarct
aberrant spinal pathways
Stroke
Why do CF patients get pneumothoraces ?
Endobronchial obstruction due to accumulation of viscous secretions, air trapping and over pressure in alveolar causes them to pop
What is the risk of PTX in CF patients ?
3% ; mortality 6-14 %
How do we treat PTX in CF patients ?
Will always need a drain ; VATs if surgery needed , try to avoid chemical Pleurodesis as difficult to transplant
Cover with abx
What percentage of CF patients get pancreatic insufficiency?
85%
30% will become diabetic
What percentage of CF patients will have liver problems ?
20% ; 6-8% will have established cirrhosis
All <20 years
What cancers are more common in CF patients ?
X6 increase risk of GI cancers , occur at younger age
Should have colonoscopy every 5 years
What percentage of CF patients have diabetes ?
40% @ 40 years
What are the classes of CFTR mutations
Class I-III No residual CFTR function
Class IV-VI Some residual CFTR function
Class II F508 del most common - defective protein maturation and trafficking
Outline the classes of CFTR mutation
Class I : Defective protein synthesis (G542X)
Class II: Defective protein maturation and trafficking (F508del)
Class III: Impaired chloride channel opening (G551D)
Class IV: Defective channel ion transport (conductance)R117H
Class V: Defective splicing
Class VI: Accelerated turn over at cell surface
What is bronchial dilatation suggested by ?
Bronchoarterial ratio >1
Lack of tapering
Airway visibility within 1cm of costal pleural surface or touching mediastinal pleura
What are indirect signs commonly associated with bronchiectasis ?
Bronchial wall thickening
Mucous impaction
Mosaic perfusion / air trapping on expiratory CT
What treatment should be used in non Pseud colonised Bronchiectasis patients that are exacerbating ≥ 3 per year
Azithromycin (250mg x3 per we week)
Doxy is an alternative
What treatment should be used in Pseud colonised Bronchiectasis patients that are exacerbating ≥ 3 per year
Inhaled Colistin
(Inhaled Gent is a 2nd line)
If cont to have high exacerbation frequency can consider azithromycin as an addition
If 5 or more exacerbations despite the above then regular IV abx every 2-3 months
What is the advice with long term aminoglycosides ?
Avoid if CrCl <30
Caution if hearing loss
Avoid concomitant nephrotoxics
Needs challenge test prior
In which bronchiectasis patients do we consider cyclical abx ?
Those with 5 or more exacerbations per year despite optimal tx
Which bronchiectasis patients get PR?
Those with MRC ≥ 2 (mMRC ≥ 1)
Which bronchiectasis patients get surgery ?
Those with localised disease where symptoms are not controlled by medical treatment optimised
What are the criteria for transplant for bronchiectasis ?
<65 and FEV1 <30% with significant clinical instability
Consider earlier referral if :
- massive haemoptysis
- severe secondary pulmonary HTN
- ICU admission
- Resp failure
What is first line eradication therapy for Pseudomonas in Non CF bronchiectasis ?
Ciprofloxacin 500mg or 750mg BD for 2/52
Second line :
IV Beta lactase +/- IV aminoglycoside for 2/52 followed by 3/12 of nebulised colistin , gentamicin or Tobramycin
With patients with bronchiectasis and CVID or x Linked agammaglobulinaemia how would you treat ?
Offer IgG treatment
What ix should all bronchiectasis patients have ?
FBC, serum immunoglobulins, serum IgE and Aspergillus specific IgE
Outline PCD
Autosomal recessive disorder
usually diagnosed in childhood
Incidence 0.9-10.3%
Nasal nitric oxide levels are abnormally low in PCD
Fx of PCD: Otitis media , male infertility , situs invertus
