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KirsiMalmivaara

Cystic Fibrosis (CF)

Essentials

  • In a setting where neonates are not screened for cystic fibrosis (as is the case in Finland), the disease should be kept in mind as a diagnostic alternative:
    • in neonates with meconium ileus
    • in neonates doing poorly, with low weight gain, diarrhoea and electrolyte disturbances
    • in children with respiratory symptoms, such as recurrent chesty cough and a vicious circle of respiratory infections.
  • The diagnosis is based on a sweat test and genetic tests. A normal sweat test does not exclude the possibility of CF.
  • A faecal elastase test will only reveal pancreatic exocrine insufficiency. A normal result will not exclude the possibility of CF.
  • CF should be treated at a specialized unit, and a physician specialized in the treatment of CF should be consulted for every exacerbation.
  • Asthma medicines should not be used to treat CF unless the patient also fulfils the diagnostic criteria for asthma.

Epidemiology and aetiology

  • Cystic fibrosis (CF) is in the white population the most common recessively inherited metabolic disease affecting multiple organs. It is caused by a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7.
    • The gene codes for a chloride ion channel protein regulating the amount of fluid in the mucous membranes.
    • More than 1 800 mutations causing the disease have been described.
  • There are more than 70 000 people with cystic fibrosis worldwide.
  • In Finland, CF is rare, with an incidence of about 1:25 000 and a prevalence of 1:50 000. Its incidence worldwide varies, being clearly higher in other western countries; in Great Britain, for instance, it is 1/2 500.

Pathogenesis

  • The manifestation of cystic fibrosis depends on the type of gene mutation involved. Gene defects are divided into 6 classes depending on the CFTR channel protein dysfunction caused by the defect.
    • Class 1: A faulty stop codon stops protein production prematurely, completely preventing the production of functional CFTR protein.
    • Class 2: Protein folding is abnormal, and only a part of the protein reaches the cell membrane; in addition, the function of the channel is defective.
    • Class 3: The channel protein reaches the cell membrane normally but, due to a protein defect, the channel does not open up to allow chloride ions to flow out of the cell.
    • Class 4: The protein reaches the cell membrane and the channel opens up normally but, due to the protein defect, the channel cannot let ions through as well as a protein working normally.
    • Class 5: The protein as such functions normally on the cell membrane but its quantity is reduced.
    • Class 6: The protein reaches the cell membrane normally and functions normally but due to the defect it is removed too quickly from the membrane.

Clinical picture

  • The clinical picture of the disease depends on the type of mutation and on the patient's age. In classes 1-2, the clinical picture is usually more severe, and in classes 3-6, it may be milder.
  • Meconium ileus is the most common first manifestation of CF; this is found in 20% of patients with CF.
  • Other symptoms seen in the neonatal period are poor weight gain and growth, steatorrhoea and electrolyte problems.
  • Pulmonary symptoms are the most common manifestation of CF. These include chronic chesty cough, abnormal sticky mucus in the respiratory tract, obstructive breathing, dyspnoea, impaired exercise tolerance and recurrent bacterial and fungal lung infections.
  • The most common associated disease is pancreatic insufficiency occurring in 85% of patients with CF worldwide and in 96% of child patients in Finland. Pancreatic insufficiency causes malabsorption of nutrients and fat-soluble vitamins.
  • Other associated diseases include CF liver disease (CFLD), CF-related diabetes (CFRD), nasal polyposis and recurrent sinusitis, osteoporosis, arthritis and, in men, aspermia due to a lack of seminiferous tubules.

Diagnosis

  • The sweat test is the most important diagnostic test. In the test, following stimulation by pilocarpine iontophoresis, the electrical conductivity of sweat, reflecting the sweat electrolyte concentration, is measured and expressed as the total electrolyte concentration (mmol/l).
    • Values below 30 mmol/l are interpreted as normal.
    • Values between 30 and 60 mmol/l are in the grey zone.
    • Values exceeding 60 mmol/l are abnormal.
    • Even a normal test result will not completely exclude the possibility of CF.
  • In a genetic test, mutations associated with cystic fibrosis are sought. In the Helsinki region in Finland, a test including the 50 most common mutations in Europe is used. Many commercial tests can find a significantly higher number of mutations.
  • The faecal elastase test detects the possibility of CF-related pancreatic insufficiency.

Treatment and prognosis Long-Term Oral Steroids for Cystic Fibrosis, Omega-3 Fatty Acids (from Fish Oils) for Cystic Fibrosis, Inhaled Bronchodilators for Cystic Fibrosis, Oxygen Therapy for Cystic Fibrosis, Oral Calorie Supplements for Cystic Fibrosis, Non-Invasive Ventilation for Cystic Fibrosis, Positive Expiratory Pressure Physiotherapy for Airway Clearance in People with Cystic Fibrosis, Topical Cystic Fibrosis Transmembrane Conductance Regulator Gene Replacement for Cystic Fibrosis-Related Lung Disease, Oscillating Devices for Airway Clearance in Cystic Fibrosis, Sodium Channel Blockers for Cystic Fibrosis, Prophylactic Anti-Staphylococcal Antibiotics for Cystic Fibrosis, Once-Daily Dosing of Aminoglycosides for Cystic Fibrosis, Drug Therapies for Reducing Gastric Acidity in People with Cystic Fibrosis

  • The treatment of pulmonary disease is based on the following:
  • Other treatments include pancreatic enzyme replacement (Creon® ), vitamin A, D, E and K supplementation and, as necessary, dietary supplements.
  • High-dose ibuprofen may slow down the impairment of lung function in children but is not often used due to its adverse effects.
  • Treatment should be carried out at a specialized unit with a multiprofessional team including, in addition to physicians, a CF nurse, physiotherapist, therapeutic dietitian and a social worker or psychologist.

Prognosis

  • According to the global CF Foundation's patient register, in the USA the life expectancy of patients with CF was 44 years in 2017.
  • Compared with this estimate, the prognosis will probably be significantly improved with new pharmaceuticals.

References

  • Marcus A. Mall and J. Stuart Elborn (toim.). Cystic fibrosis. ERS Monograph. European Respiratory Society, 2014. DOI 10.1183/1025448x.erm6414 http://books.ersjournals.com/content/cystic-fibrosis
  • Castellani C, Duff AJA, Bell SC et al. ECFS best practice guidelines: the 2018 revision. J Cyst Fibros 2018;17(2):153-178. [PubMed]

Evidence Summaries ⬆