Cystic Fibrosis

Genetic disease which leads to abnormally viscous mucus; mucus blocks many structures including the conducting airways and lungs - results in repeated chest infections and chronic colonisation

Aetiology

  • Autosomal recessive mutation involving the material that codes for the cystic fibrosis transmembrane regulatory (CFTR) protein
    • Carrier rate 1/25 in UK
  • Most common in Caucasians

Pathophysiology

  • CFTR protein normally forms a channel on mucosal surfaces that allows chloride ions out of the cell and into the lumen (e.g. lumen of airway)
  • In the lungs and GI tract, failure of CFTR results in reduced Cl- secretion into the lumen
    • Na+ normally follows Cl-so Na+ secretion is also reduced
    • Less Na+ in lumen = increased water reabsorption from lumen into epithelial cells
    • Results in a viscous mucus which blocks ducts and impairs mucosal defense
  • In the sweat glands, failure of CFTR results in excess Cl- (and Na+) in the sweat
  • Mutations have been divided into different classes, depending on their effect on CFTR
  • Pseudomonas infections is associated with worse prognosis
    • By adulthood most patients will have a chronic Pseudomonas infection with a unique strain of Pseudomonas - adults with CF advised not to mix

Clinical presentation

  • Classical presentation - child aged 0-2 with recurrent infections, large offensive stools and failure to thrive
  • Older at diagnosis = more S+S

Respiratory symptoms

  • Recurrent respiratory infections
  • Chronic daily cough and sputum production
  • Dyspnoea
  • Nasal polyps
  • Haemoptysis

Gastrointestinal symptoms

  • Failure to thrive in infancy and low body mass index in adults
  • Meconium ileus in infancy
  • Distal intestinal obstruction syndrome in YAs
  • Voracious appetite in kids
  • Malabsorptive stool with steatorrhoea due to pancreatic insufficiency
  • Also gallbladder stones, cirrhosis

Other symptoms

  • Salty sweat
  • Infertility in males - bilateral absence of vas deferens
  • CF-related diabetes

Signs

  • Cyanosis
  • Clubbing
  • Chest hyperinflation
  • Bilateral coarse crackles

Investigations

  • Sweat test - diagnostic
  • Genetic testing for CFTR mutations

Management

Respiratory problems

  • In the early, pre-infected stages, mucus clearance, preventing infection and maintaining good lung function are the main aims
  • Chest physiotherapy should be given twice-daily
  • Regular sputum samples are sent for bacterial culture
  • Prophylactic antibiotics - often prophylactic agent to reduce staph. aureus (e.g. flucloxacillin)
  • CFTR modulators are relatively new drugs which improve flow through CFRT - ivacaftor, orkambi, symkevi, trikefta
  • Consider lung transplant once FEV1 <40%

Management of non-respiratory complications

  • Pancreas - CREON for exocrine failure, diabetes monitoring for endocrine failure
  • Bowels - mucous blocks intestine (DIOS), prevent/treat with laxatives, fluids and hydration
  • Liver - TIPSS for portal hypertension (hepatic ducts become blocked)
  • Dietician - to ensure adequate nutrition and hydration

Management of an exacerbation

  • Increase chest physiotherapy
  • Add two weeks of antibiotics appropriate to the most recent sputum sample