The most common inherited genetic condition in N European populations, with carrier rate of 1 in 20. Incidence is therefore around 1 in 4000 births. Most common gene defect is deletion at delta F508 of CFTR (CF transmembrane conductance regulator) gene.

Features:

• family history
• congenital intestinal atresia
• meconium ileus
• distal intestinal obstruction syndrome
• faltering growth (in infants and young children)
• undernutrition
• recurrent and chronic pulmonary disease, such as:
  • recurrent lower respiratory tract infections
  • clinical or radiological evidence of lung disease (in particular bronchiectasis)
  • persistent chest X-ray changes
  • chronic wet or productive cough
• chronic sinus disease
• obstructive azoospermia (in young people and adults)
• acute or chronic pancreatitis
• malabsorption
• rectal prolapse (in children)
• pseudo-Bartter syndrome.

Median predicted life expectancy is now nearly 50 years, but this doesn’t take into account the new CFTR modulators. Management has evolved slowly, with revolutionary improvements including high calorie diets/feeding, pancreatic enzyme replacement, specialist CF centres and CF newborn screening.

Drugs

• Regular prophylactic antibiotics (usually starting with oral flucloxacillin) introduced at early stage. Later on may require regular courses of IV antibiotics.
• Azithromycin given on Mondays, Wednesdays and Fridays – but for anti-inflammatory properties as much as antibacterial.
• Creon is the name for pancreatic enzyme supplements, taken with each meal.
• Fat soluble vitamins.
• Nebulised DNAse and hypertonic saline to help with chest physiotherapy

New treatments

CFTR modulators treat the basic defect. Lead to significantly improved pulmonary function, decreased respiratory infections and improved nutrition.

Combination elexacaftor, tezacaftor and ivacaftor, will be suitable for approximately 90% of all people with CF. But expensive, with many countries unwilling or unable to fund them.

CFTR phenotypes vary. Class I–III variants are most severe, with minimal or no CFTR function. Class IV–VI variants are where CFTR is produced and reaches apical membrane but doesn’t work normally, so milder phenotype.

Ivacaftor reduces hospital admission, rates of respiratory Pseudomonas and Aspergillus infection, and halves rate of decline in FEV1 %, suggesting at least 5 years survival benefit.

[http://dx.doi.org/10.1136/archdischild-2020-320680]