Cystic fibrosis

Last revised by Rohit Sharma on 20 May 2024

Cystic fibrosis (CF), also called mucoviscidosis, is an autosomal recessive genetic disease that affects the exocrine function of the lungs, liver, pancreas, small bowel, sweat glands, and urogenital system.

This article is a general discussion of the disease. Each organ system are discussed separately, see:

Cystic fibrosis is the most common genetic disease affecting European population with an incidence of approximately 1:2000-3500 live births 5.

The diagnosis may be suspected antenatally due to the presence of echogenic bowel on antenatal ultrasound, or due to genetic testing of the parents.

In many countries, the presence of cystic fibrosis is tested for immediately after birth with a sweat test (positive sweat chloride test Cl >60 mEq/L) 5. Alternatively, genetic testing is also available.

The diagnosis usually becomes evident in infancy, with presentations including 12:

Cystic fibrosis is an autosomal recessive inherited genetic disorder that results from a homozygous defect of the cystic fibrosis transmembrane regulator (CFTR) gene on chromosome 7q31.2. The gene encodes for the corresponding CFTR protein, which regulates chloride ion transport across cell membranes. There are over 2000 mutations of the CTFR gene identified to date, with the most common being delF508 (deletion of the codon for phenylalanine at the 508 position) affecting 66% of cases 6,14.

CFTR gene mutations are classified into 6 categories based on the synthesized protein structure and function as follows 14,15,17:

  • class I: mutations resulting in premature stop codons; CFTR expression is severely reduced or absent

  • class II: mutations resulting in CFTR misfolding and increased degradation; functional CFTR reacting the cell surface is reduced

  • class III: mutations that impair regulation of the CFTR channel; abnormal gating with reduced opening

  • class IV: mutations that impair CFTR ion conductance

  • class V: mutations of CFTR promotor or splicing; CFTR protein is normal in structure and function, but reduced in number

  • class VI: mutations that reduce stability of CFTR; increased turnover of CFTR and reduced duration at the cell surface

The precise way in which CFTR mutations cause disease is complex and still under investigation. However, the most widely accepted explanation is that these mutations reduce extracellular chloride ion transport, leading to production of abnormally thickened mucus and eventual organ dysfunction 14,15. This is now known to be an oversimplification, as it has been shown that the CFTR protein also regulates the transport of sodium, bicarbonate, and glutathione 15.

Unlike in other tissues, CFTR in sweat glands function in the opposite way, responsible for intracellular chloride ion transport 16. In patients with cystic fibrosis, the CFTR mutation results in excess chloride, sodium and fluid loss onto the skin surface, hence the use of the sweat test for diagnosis 16.

Early treatment is essential and responsible for the dramatic increase in life expectancy, now reaching 40 years or more.

Treatment options include 7,10,13:

  • dietary changes, including pancreatic enzyme and vitamin supplementation

  • physiotherapy and airway clearance techniques

  • cystic fibrosis transmembrane regulator (CFTR) modulators

    • for delF508 mutation:

      • ivacaftor and lumacaftor combination therapy

      • ivacaftor and tezacaftor combination therapy

      • elecacaftor-tezacaftor-ivacaftor combination therapy

    • for G551D mutation: ivacaftor monotherapy

  • anti-inflammatory therapy (e.g. azithromycin)

  • antibiotics, often multiple agents administered for prolonged courses

  • oral and inhaled corticosteroids

  • lung transplantation

  • specific management of complications (e.g. diabetes mellitus, hemoptysis, distal intestinal obstruction syndrome (DIOS), etc.)

Both transplanted and non-transplanted patients with cystic fibrosis are at increased risk of some malignancies 8:

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