Cystic Fibrosis in children and adults

Question 1

Is cystic fibrosis common?

Answer 1

Cystic fibrosis is the commonest inherited, life-shortening, disorder amongst N. European populations.

• Inherited as an autosomal recessive trait.
• Gene prevalence = 1:25

Question 2

Features of the Cystic Fibrosis Gene

Answer 2

• Lies on the long arm of chromosome 7
• Cystic fibrosis transmembrane conductance regulator (CFTR)
• Different mutations can result different phenotype of disease: 6 classes, commonest phe508del.

Question 3

Functions of the CFTR gene

Answer 3

• Cilial collapse: Active transport channel for chloride (HCO3), regulates liquid volume on epithelial surface = reduced chloride (HCO3) efflux, increased sodium influx via ENaC.
• Excessive, innate inflammation
• Thick sticky mucus

Question 4

Pathophysiology of airway epithelia

Answer 4

Traps organisms, chronic infection, excessive DNA from neutrophil apoptosis.

Question 5

Presenting features of cystic fibrosis in antenatal

Answer 5

common: CVS, Echogenic bowel

Less common: Perforated meconium ileus

Question 6

Presenting features of cystic fibrosis in neonatal

Answer 6

Common: Screening, Mec ileus (10%)

Less common: Gut atresia, obstructive jaundice, Vitamin deficiencies

Question 7

Presenting features of cystic fibrosis in infants and young children

Answer 7

Common: Recurrent chest infections, Failure to thrive

Less common: Rectal prolapse, Pseudo-Bartter’s syndrome, Anaemia, oedema, hypoproteinaemia

Question 8

Presenting features of cystic fibrosis in older children and adults

Answer 8

Common: recurrent chest infections, Nasal polyps and sinusitis, Male infertility

Uncommon: Acute pancreatitis, Liver disease, Pseudo-Bartter’s, Atypical mycobacteria

Question 9

How to make a diagnosis for CF in children

Answer 9

• Clinical assessment
• Sweat test (chloride)
• Repeat CF mutation analysis

Question 10

Antenatal screening (following identification of CF patient)

Answer 10

• Pre-implantation genetic diagnosis
• Chorionic villus sampling
• Amniocentesis

Question 11

Management methods of cystic fibrosis

Answer 11

• Multi-organ disease: specialist multi-disciplinary team (improved long-term outcome)
• Shared care with local clinics
• Primary care: surveillance, early treatment of infection

Question 12

What are the two cardinal features of CF?

Answer 12

• Pancreatic insufficiency (85-90%): abnormal stools, failure to thrive.
• Recurrent bronchopulmonary infection: pneumonitis, bronchiectasis, scarring, abscesses.

Question 13

Treatment of pancreatic insufficiency

Answer 13

• Enteric coated enzyme pellets
• High energy diet: low fat
• Fat-soluble vitamin and mineral supplements

Question 14

What is the vicious cycle of CF lung disease?

Answer 14

Mucus obstruction, infection&raquo_space; Infection (chronic)&raquo_space; Increased inflammation&raquo_space; Fibrosis/scarring/bronchiectasis

Question 15

Therapeutic targets for mucus obstruction, inflammation

Answer 15

Airway clearance physiotherapy, Dornase alfa, Hypertonic saline

Question 16

Therapeutic targets for infection (chronic)

Answer 16

Antibiotics

Question 17

Therapeutic targets for increased inflammation

Answer 17

Azithromycin

Question 18

Common respiratory pathogens in CF

Answer 18

• Staphlococcus aureus and Haemophilus influenzae in early years
• Pseudomonas aeruginosa in later years

Question 19

Less common respiratory pathogens in CF

Answer 19

• Burkholderia cepacia
• Stenotrophomonas maltophilia
• MRSA
• Atypical mycobacteria e.g. M abscessus
• Lung microbiome

Question 20

CF - respiratory tract infections

Answer 20

• Early years: Pre-infection, eradication of early infection (80-90%)
• Chronic infection (usually Pa, Sa and Hi)
• Reduce inflammation: Ibruprofen, azithromycin, prednisolone

Question 21

Other manifestations/complications of CF

Answer 21

• GI: dysmotility, co-existent disease
• Hepatopathy
• Upper airway polyps and sinusitis
• Dysglycaemia (diabetes): more common in adults
• Bones: Osteopenia, Arthropathy
• Heat exhaustion
• Bilateral absence of vas deferens
• Vaginal candidiasis, stress incontinence

Question 22

What are social, educational and economic impacts on child and family due to CF?

Answer 22

• Barriers to making friends
• Increased depression/anxiety
• Low adherence to time-consuming treatments
• Increased costs to the family