Cystic Fibrosis

Question 1

Cystic Fibrosis: What is the incidence of carrier of CFTR mutation and what is the incidence?

Answer 1

1/25 has the gene

1/2500 has the disease (Caucasian)

Question 2

What are the clinical manifestations of CF? (and symptoms to ask for in history)

Answer 2

Respiratory:

nasal polyps, recurrent sino-pulmonary disease, airway obstruction, bronchiectasis, ABPA, cor-pulmonale.

GIT: distal bowel obstruction - almost always in hot weather (As they are dehydrated and bowel mucus becomes thickened), GORD (100%, due to failure to neutralise gut secretion by pancreas → creates vicious cycle as it makes respiratory illness worse). Rectal prolapse.

HPB: Thick bile → cholestasis due to IHD congestion → biliary cirrhosis (10% of CF) + portal HTN, fat soluble deficiency. Exocrine insufficiency → vitamin deficiency. Pancreatitis.

Endo: Diabetes

Genitourinary: male infertility, female infertility (rare), amenorrhoea (common)

Psychiatry: insight, adherence problems

Question 3

Cystic fibrosis - how is the diagnosis made?

Answer 3

Sweat chloride is the most important diagnostic test.

Sweat Cl- ≥70mmol/L diagnostic (still do CFTR)

If 40-60 - intermediate (or <40 but strong clinical suspicioun) → repeat sweat test + CFTR sequencing.

If no or only 1 CF-causing variants detected on sequencing, repeat sweat test + do expanded DNA sequencing to detect other potential variants.

If 2 CF-causing variants found, it confirms the diagnosis.

Question 4

Cystic fibrosis history

Answer 4

P: date dx, symptoms, systems (resp, GIT, HPB, Endo, GU)

• SOB, cough, recurrent infections
• Bowel obstruction
• Steatorrhoea, diarrhoea, malabsorption / vitamin deficiencies
• Jaundice and Liver cirrhosis
• Diabetes
• Infertility / Amenorrhoea

R: FH (autosomal recessive)

I: How was the diagnosis made (Sweat test, CFTR sequencing or clincal), sputum MCS (?Pseudomonas), Lung function test

C: haemoptysis (60% minor, ≤250mls, 7% major - _bronchial artery embolisatio_n?), recurrent pneumonia, ICU admissions, pneumothorax (had pleurodesis? if yes, contraindication for transplant), Cor-pulmonale

Management of…

• Disease - chest PT (how often, and who - PT or family), what techniques do you use? (deep breathing, postural drainage, percussion/vibration, “huffing”, PEP device). Ivakaftor, Lumikaftor. Chronic ABx. Was the transplant discussed?
• Complications - Insulin (if diabetic), dietician, Creon, Vitamin supplementation, PEG

Current status & Compliance

• Admissions last 12 months. Current ET.
• How often followed-up & what is the most pressing issue currently.
• How is it impacting the patient - work, family, fertility / relationships
• Adherence to therapies and why not

Prognosis

• How do you think your CF is going? What is your understanding of complications / prognosis of CF?

Question 5

What is your approach to investigating this patient with Cystic Fibrosis?

Answer 5

T: Swat test, CFTR sequencing

E: infection - review previous sputum MCS (for colonising micro-organisms) and repeat one, septic work-up (bloods, culture, CXR…etc)

S: inflammatory markers, FBC (ACD, polycythaemia), ABG, spirometry/PFT (FEV1 >40% = poor prognosis), imaging (CXR - rule out PTX, previous pleurodesis or CT - bronchiectasis, burden of disease)

Screen complications: Fasting glucose, OGTT (not HBA1C in CF), LFT (cholestasis, if abnormal as per Cirrhosis investigations), fecal elastase (pancreatic insufficiency), fertility history, AXR (obstruction/constipation)

Question 6

What are common colonising bacteria in CF patients? (5) Which one has the worst prognosis? (2)

Answer 6

Staph aureus

H. influenzae

Pseudomonas aereginosa

Mycobacterium absessus - worse outcome, contraindication for lung transplant in most

Burk-old-heria cerpacia - very, very bad, effectively 100% mortality

Question 7

What is your approach to managing this patient with CF?

Answer 7

Goals:

• slow disease progression
• prevent acquisition of resistant bacteria
• improve compliance***
• prevent complications

Confirm dx: typical phenotypic criterion (sinopulmonary disease or GI or salt loss or azospermia), sweat test, CFTR sequencing for genotype. If was picked up on neonatal screening, was the dx confirmed by sweat Cl- and genotype?

A: screen for associated comorbidities & complications

• Bronchiectasis, sputum MCS for colonisation - 3 monthly
• Diabetes (OGTT/fasting glucose)
• Exocrine insufficiency (fecal estalase)
• Biliary cirrhosis (LFTs if abnormal, work-up with USS liver, doppler and MRCP). Occurs early, hence most LC patients would have had liver transplant if they did have cirrhosis
• Cor-pulmonale (TTE)
• Depression

T: Non-pharm

• Difficult Mx problem that requires continued support and encouragement
• Educate: importance of adherence in preventing complication and early mortality, especially in light of improving prognosis
• Chest PT: daily, flutter valves, PEP device. Suggest Acepella device which combines PEP and vibration. Educate on techniques - huffing, postural drainage and percussion techniques if not done already.
• Dietician involvement, High-Calorie diet, Vitamin supplementation, pancreatic enzyme supplements (Creon)
• consider nocturnal NG or PEG feeds
• Infection prevention - vaccinations, hand/food hygiene
• CF support groups

T: Pharm

• Decrease airway obstruction & reactivity → salbutamol/atrovent
• Mucolytics - consider hypertonic saline or DNAse (slows decline in lung function)
• Decrease microbial load → Azithromycin 250mg OD. If MSSA (Fluclox 1m), Pseudomonas (nebulised tobramycin / colistin alternating 1 monthly)
• Pseudomonas exacerbation - 2 x IVABs
• Targetted therapy: Ivakaftor (G551D), Lumikaftor/Ivakaftor (for delta F508)
• Transplant if hypoxia, hypercapnoea or FEV1 <30%
• Insulin for T1DM.
• Liver Cirrhosis - ursodeoxycholic acid (low-evidence), transplant

Involve GP/Famil/Support group to ensure continued support and encouragement

Ensure FU and screen for complications

• Monitor progress of lung function: spirometry, PFT, Sputum MCS 3 monthly - assess the need for transplant. TTE for pulmonary HTN (consider transplant)
• SGA and look out for evidence of malnutrition
• Regular OGTT, screen for depression
• Early identification & treatment of infection

Question 8

What are the indications for lung transplant in CF?

Answer 8

FEV1 <30%

Rapidly declining lung function (even if >30%) and any of

1. Increasing O2 requirement
2. Hypercapnoea
3. Pulmonary HTN

Question 9

Does CF recur in transplanted lung? What is the prognosis (5-y survival rate)?

Answer 9

No, it does not.

5-year survival is 65%

Question 10

Nutrition advice for CF patient who had a transplant?

Answer 10

Safety: avoid undercooked food, soft cheeses, and unpasteurized milk (Listeria)

DIOS (distal intestinal obstructive syndrome): main Mx is hydration, Creon. Not surgery. Watch opioids.

Question 11

Cystic fibrosis - what are multisystemic manifestations & it’s management long-term?

Answer 11

Top-down:

1. Sinus disease: saline rinses, nasal steroids, mechanical clearance with saline, surgical intervention
2. Liver disease (33%): Cirrhosis (10% - mostly pre 20s. Most long case-patient would have already had liver transplant). Treat with urso-falk (low-evidence)
3. Pancreatic insufficiency (85%): Creon, TIDM Mx.
4. Nutrition:
5. Fertility & family planning: azoospermia. Needs sperm harvesting. Need to refer to genetic counseling, fertility clinic.

Gold - mention & ask about impact on the child. Do they know that there is some possibility that they may not be alive when their child is 10 year old? (5-y survival post lung transplant 80%, less in 10 years). How would this affect your partner?

6. Cancer risk (in transplants): 10-fold risk of CRC and 5-fold UGI cancers, 20-fold risk of SB cancer
7. Mental health: requires annual psychology review

Question 12

Why is it important to know whether CF patient DM prior to transplant or not?

Answer 12

If developed before transplant - it is CF-related DM, where treatment would be insulin.

If NODAT - as per TIIDM Mx.