Cystic fibrosis

[Ghada Abdullah]

Cystic Fibrosis - an autosomal recessive disease affecting 1 in 2500 births in the Caucasian population and carrier rate is 1 in 25. It occurs due to a gene mutation on chromosome 7 (at ?F508 in 78% of UK CF patients). This is the gene which codes for the cystic fibrosis transmembrane regulator (CFTR) which is defective in CF. CFTR acts as a cyclic-AMP activated chloride channel blocker. Abnormal ion transport across the epithelial cells of the exocrine glands of the respiratory tract and pancreas results in abnormally thick secretions. Abnormal function of the sweat glands results in excessive concentrations of sodium and chloride in the sweat (80-125 mmol/L in CF, 10-14mmol/L in normal children). This forms the basis of diagnosis via a sweat test (2 positive required due to false positives). Most children with CF present with malabsorption, failure to thrive and recurrent chest infections caused by the viscid fluid providing a pool for chronic superinfection by bugs such as Staph aureus, Haemophilus influenza, and pseudomonas. The child has a persistent lose cough with purulent sputum, air trapping, coarse creps and with established disease, finger clubbing and chronic hyperinflation. Approx 10-20% present in infancy with meconium ileus. Over 90% have malabsorption and steatorrhoea due to insufficiency of the pancreatic exocrine enzymes (lipase, amylase and proteases). Management is via MDT team with 2-4 x day chest physiotherapy, continuous oral antibiotics with prompt IV antibiotics to limit lung damage. Nebulised antibiotics and mucolytics may be used in chronic infection. 1/3 have reversible airways obstruction that benefit from bronchodilators. Dietician involvement is essential with pancreatic enzyme supplements and a high calorie diet. Screening is now part of the Guthrie Test in some areas, however this only covers the common UK mutations.
Clinical features of CF:
Respiratory:
- recurrent chest infections
- bronchiectasis
- pneumothorax
- sinusitis
- nasal polyps
- haemoptysis
- aspergillosis
Gastrointestinal
- steatorrhoea
- malabsorption - failure to thrive
- meconium ileus
- rectal prolapse
- DIOS (distal intestinal obstruction syndrome)
- cirrhosis and portal hypertension
- diabetes mellitus (late)
Others:
- sterility in males (obstructed vas deferens)
- psychological