Cystic fibrosis

Last revised by Fergus O'Herlihy on 7 Nov 2023

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 the male genital system. This is resulting in progressive disability and multisystem failure.

This article is a general discussion of the disease. Each organ system will be discussed separately.

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 due to a homozygous defect of the CFTR gene located on chromosome 7q31.2. This gene encodes for a transmembrane protein known as cystic fibrosis transmembrane regulator (CFTR) which is responsible for regulating chloride passage across cell membranes. There are at least 6 classes of mutations, the commonest being ∂F508 (66-70%) 6.

In skin, unlike elsewhere, the CFTR protein is responsible for the influx of chloride and increases the sodium channel activity, thus controlling the influx of sodium. The net effect of a normally functioning CFTR is to resorb sodium and chloride. In CF patients, this is lost and therefore the characteristic increase in salt content of sweat (thus the sweat test).

In tissues other than skin, the CFTR protein is responsible for efflux of chloride and inhibition of the sodium channel's activity which controls the influx of sodium. Therefore, under normal circumstances, salt and chloride remain in the lumen and keep water there osmotically. In CF patients, too little chloride is pumped out, too much sodium is resorbed with osmotic resorption of water from the lumen. The result is iso-osmotic, but low volume, secretions, which tend to dry out, or be thick as they still contain all the other constituents.

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

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 ∂F508 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 CF patients are at increased risk of some malignancies 8:

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Cases and figures

  • Figure 1: finger clubbing in cystic fibrosis
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  • Case 1
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  • Case 2: with pancreatic calcification
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  • Case 3
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  • Case 4: with meconium ileus
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  • Case 5
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  • Case 6: mucous plugging
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  • Case 7: with DIOS
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  • Case 8
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  • Case 9: with left upper lobe collapse
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  • Case 10
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  • Case 11
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  • Case 12
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  • Case 13
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  • Case 14: middle lobe pneumonia, mucous plugging and bronchiectasis
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  • Case 15
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