Cystic Fibrosis and Bronchiectasis

Question 1

What is the approximate median life expectancy for homozygous F508-del cystic fibrosis?

Answer 1

UK median survival of 46 years for males and 41 years for females in homozygous F508-del cystic fibrosis sufferers

Question 2

In adults who should we consider investigating for CF?

Answer 2

• 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

Question 3

How is CF diagnosed ?

Answer 3

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

Question 4

What are the complications of CF?

Answer 4

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)

Question 5

What are the mucoactive agents used in CF?

Answer 5

Dornase Alpha - first choice, if inadequate response with dornase alone can add in Hypertonic saline

If unable to use can think about mannitol

Question 6

Outline Staph Aureus infection in CF

Answer 6

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

Question 7

Outline approach to Pseudomonas Aeruginosa in CF patients

Answer 7

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

Question 8

If CF pt on colistin nebs but still deteriorating due to Pseud , what can be trialled ?

Answer 8

Aztreonam
Nebulised Tobramycin
Tobramycin DPI

Question 9

Outline DIOS

Answer 9

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

Question 10

What should make you think of CF diabetes ?

Answer 10

Increased weight loss, reduced lung function, increased frequency of exacerbations, excess tiredness

Question 11

What is Kaftrio?

Answer 11

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

Question 12

What is Symkevi?

Answer 12

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

Question 13

What is Orkambi?

Answer 13

• Ivacaftor and Lumacaftor
  (IL)
• two copies of F508 del mutation
• slows decline in lung function

(Approx 50% have mutation)

Question 14

What is Kalydeco?

Answer 14

Ivacaftor

Effective in anyone with one of nine gating mutations
(Improvement in lung function and reduction in sweat chloride levels)

Question 15

Outline the genetics for CF

Answer 15

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

Question 16

What is the carrier rate for CF in UK?

Answer 16

1 in 25

Question 17

What is the live birth rate of CF in UK?

Answer 17

1 in 2500

Question 18

How do you interpret sweat test results ?

Answer 18

<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

Question 19

What is the dominant pathogen for CF patients in childhood ?

Answer 19

Staph Aureus

Question 20

What is the dominant pathogen for CF patients in teens/adulthood ?

Answer 20

Pseudomonas

Question 21

What is the Leeds Criteria ?

Answer 21

Chronic Pseudomonas Aeurginosa infection as >50% samples +ve in last 12 months

Question 22

What are the issues with P.Aeurginosa colonisation in CF?

Answer 22

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)

Question 23

How do we eradicate P.Aeruginosa in CF?

Answer 23

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

Question 24

Do we treat chronic Pseud colonisation in CF?

Answer 24

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

Question 25

Outline Burkholda Cepacia

Answer 25

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

Question 26

Outline M. abscessus in CF

Answer 26

Accelerated lung function decline, multi resistant to eradication and contraindication to lung transplant

Question 27

Which drugs affect CFTR Function?

Answer 27

Ivacaftor

Question 28

Which drugs affect CFTR quantity ?

Answer 28

Tezecaftor Elexacaftor Lumacaftor

Question 29

Outline Haemoptysis as complication in CF

Answer 29

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

Question 30

What are the risks of bronchial artery embolisation?

Answer 30

Chest pain Inflammation and exacerbation Pulmonary infarct aberrant spinal pathways Stroke

Question 31

Why do CF patients get pneumothoraces ?

Answer 31

Endobronchial obstruction due to accumulation of viscous secretions, air trapping and over pressure in alveolar causes them to pop

Question 32

What is the risk of PTX in CF patients ?

Answer 32

3% ; mortality 6-14 %

Question 33

How do we treat PTX in CF patients ?

Answer 33

Will always need a drain ; VATs if surgery needed , try to avoid chemical Pleurodesis as difficult to transplant Cover with abx

Question 34

What percentage of CF patients get pancreatic insufficiency?

Answer 34

85% 30% will become diabetic

Question 35

What percentage of CF patients will have liver problems ?

Answer 35

20% ; 6-8% will have established cirrhosis All <20 years

Question 36

What cancers are more common in CF patients ?

Answer 36

X6 increase risk of GI cancers , occur at younger age Should have colonoscopy every 5 years

Question 37

What percentage of CF patients have diabetes ?

Answer 37

40% @ 40 years

Question 38

What are the classes of CFTR mutations

Answer 38

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

Question 39

Outline the classes of CFTR mutation

Answer 39

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

Question 40

What is bronchial dilatation suggested by ?

Answer 40

Bronchoarterial ratio >1 Lack of tapering Airway visibility within 1cm of costal pleural surface or touching mediastinal pleura

Question 41

What are indirect signs commonly associated with bronchiectasis ?

Answer 41

Bronchial wall thickening Mucous impaction Mosaic perfusion / air trapping on expiratory CT

Question 42

What treatment should be used in non Pseud colonised Bronchiectasis patients that are exacerbating ≥ 3 per year

Answer 42

Azithromycin (250mg x3 per we week) Doxy is an alternative

Question 43

What treatment should be used in Pseud colonised Bronchiectasis patients that are exacerbating ≥ 3 per year

Answer 43

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

Question 44

What is the advice with long term aminoglycosides ?

Answer 44

Avoid if CrCl <30 Caution if hearing loss Avoid concomitant nephrotoxics Needs challenge test prior

Question 45

In which bronchiectasis patients do we consider cyclical abx ?

Answer 45

Those with 5 or more exacerbations per year despite optimal tx

Question 46

Which bronchiectasis patients get PR?

Answer 46

Those with MRC ≥ 2 (mMRC ≥ 1)

Question 47

Which bronchiectasis patients get surgery ?

Answer 47

Those with localised disease where symptoms are not controlled by medical treatment optimised

Question 48

What are the criteria for transplant for bronchiectasis ?

Answer 48

<65 and FEV1 <30% with significant clinical instability Consider earlier referral if : - massive haemoptysis - severe secondary pulmonary HTN - ICU admission - Resp failure

Question 49

What is first line eradication therapy for Pseudomonas in Non CF bronchiectasis ?

Answer 49

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

Question 50

With patients with bronchiectasis and CVID or x Linked agammaglobulinaemia how would you treat ?

Answer 50

Offer IgG treatment

Question 51

What ix should all bronchiectasis patients have ?

Answer 51

FBC, serum immunoglobulins, serum IgE and Aspergillus specific IgE

Question 52

Outline PCD

Answer 52

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