Cystic Fibrosis in Children and Adults

Question 1

Describe the genetics of cystic fibrosis

Answer 1

Occur when you inherit TWO MUTATED GENES, (one from each parent)
MOST COMMON AUTOSOMAL RECESSIVE DISORDER

Question 2

How does CF occur?

Answer 2

Due to a mutation in the CFTR which is coded on chromosome 7

Question 3

CF diagnosis: antenatal testing

Answer 3

• Pre-implantation genetic diagnosis - where a cell is removed from a developing embryo and analysed.
• Chorionic villous sampling - involves removing and testing a small sample of cells from the placenta.
• Amniocentesis - a procedure in which amniotic fluid is removed from the uterus for testing or treatment.

Question 4

CF diagnosis: neonatal screening

Answer 4

Newborn bloodspot day 5 (Guthrie test)

• Screen positive - referred for clinical assessment and sweat test
• Proportion of diagnoses missed

Question 5

CF diagnosis: sweat testing any time postnatally

Answer 5

Measures the concentration of chloride excreted in sweat.

Elevated in CF.

IN CHILDREN:

• Tests usually repeated to confirm.
• Less reliable in adults and infants < 6 months old.

Question 6

3 possible diagnostic outcomes

Answer 6

• CF
• NOT CF
• CF - Screen Positive Inconclusive Diagnosis (SPID)

Question 7

CF IS A MULTISYSTEM DISEASE THEREFORE…

Answer 7

Can affect any part of the body and must be treated by a multidisciplinary team

Question 8

TREATMENT OF PANCREATIC INSUFFICIENCY IN CF =

Answer 8

BOOSTING NUTRITION

1. REPLACE ENZYMES: (CREON)
2. DIET: High energy plus high calorie supplement drinks
   **Not low fat
3. NUTRITIONAL SUPPLEMENTS: Fat-soluble vitamin and mineral supplements

Question 9

Treatment of respiratory features of CF

Answer 9

MUCUS OBSTRUCTION INFLAMMATION
- Airway clearance via physiotherapy, mucolytics bronchodilators

INFECTION (CHROIC)
- Antibiotics (oral, intravenous or nebulised)

INCREASED INFLAMMATION
- Azithromycin

FIBROSIS/SCARRING/BRONCHIECTASIS
- Supportive treatment and management of symptoms

Question 10

TWO COMMON PRESENTATIONS OF CF THROUGHOUT LIFE:

Answer 10

PANCREATIC INFUFFICIENCY

1. The CFTR mutation also affects the pancreas.
2. The pancreas produces enzymes that digest food. Lack of enzymes causes:
   
   1. Malabsorption
   2. Abnormal stools - pale, offensive, float
   3. Failure to thrive
3. Importance of records, growth charts

RECURRENT CHEST INFECTIONS

• Pneumonia
• Bronchiectasis
• Scarring
• Abscesses

Question 11

CFTR abnormality causes:

Answer 11

• abnormal electrolyte transport across cell membrane
• Dehydration of airway surface layer
• Decrease mucociliary clearance
• Mucous sticks to mucosal surface and causes shearing and inflammation
• Increase access to bacteria
• Decrease bacteria killing

Question 12

Indications a lung transplant is needed (CF)

Answer 12

• Rapidly deteriorating lung function
• FEV1 < 30%
• Life threatening exacerbations
• Estimated survival <2 years

Question 13

What are some absolute contraindications to lung transplant?

Answer 13

• Other organ failure
• Malignancy within 5 years
• Significant peripheral vascular disease
• Drug, nicotine, alcohol dependency
• Active systemic infection

Question 14

What are some relative contra-indications to transplant (where you have to use clinical judgement)

Answer 14

• Other organ dysfunction
• Non-compliance
• Steroids >20mg daily
• Absence of recognised social support
• Osteoporosis
• Low or high BMI
• Surgical risks (previous thoracic surgery)
• Psychological instability

Question 15

New modulator drug for CF

Answer 15

Addresses different parts of the CFTR production, processing, folding, transport and insertion into the membrane

Small benefits in lung function
More significant benefit is fall in chest exacerbations, rose in weight and improved QOL