Citation, DOI, disclosures and article data
At the time the article was created Frank Gaillard had no recorded disclosures.View Frank Gaillard's current disclosures
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.
pancreas (most common abdominal organ involved 9)
urogenital tract manifestations 11
bilateral seminal vesicle agenesis
hypoplasia or agenesis of the ductus deferens
hypoplasia or agenesis of the tail and body of the epididymis
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.
Treatment and prognosis
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
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:
- 1. Abbas AK, Kumar V, Fausto N et-al. Robbins and Cotran Pathologic Basis of Disease, With Student Consult Online Access. W B Saunders Co. (2010) ISBN:1416031219. Read it at Google Books - Find it at Amazon
- 2. Brant WE, Helms CA. Fundamentals of diagnostic radiology. Lippincott Williams & Wilkins. (2007) ISBN:0781765188. Read it at Google Books - Find it at Amazon
- 3. AG SK, Karger. Cystic Fibrosis, A State-Of-The-Art Series. S Karger Pub. (2001) ISBN:3805572247. Read it at Google Books - Find it at Amazon
- 4. Meyer CA, White CS, Sherman KE. Diseases of the hepatopulmonary axis. Radiographics. 20 (3): 687-98. Radiographics (full text) - Pubmed citation
- 5. Maffessanti M, Polverosi R, Dalpiaz G et-al. Diffuse lung diseases, clinical features, pathology, HRCT. Springer Verlag. (2006) ISBN:8847004292. Read it at Google Books - Find it at Amazon
- 6. Robbins SL, Kumar V, Abbas AK et-al. Robbins and Cotran Pathologic Basis of Disease. W.B. Saunders Company. (2010) ISBN:1416031219. Read it at Google Books - Find it at Amazon
- 7. Warrell DA. Oxford textbook of medicine, Sections 18-33. Oxford University Press, USA. (2005) ISBN:0198569785. Read it at Google Books - Find it at Amazon
- 8. Maisonneuve P, Marshall BC, Knapp EA et-al. Cancer risk in cystic fibrosis: a 20-year nationwide study from the United States. J. Natl. Cancer Inst. 2013;105 (2): 122-9. doi:10.1093/jnci/djs481 - Pubmed citation
- 9. Lavelle LP, McEvoy SH, Ni Mhurchu E, et al. Cystic Fibrosis below the Diaphragm: Abdominal Findings in Adult Patients. (2015) Radiographics : a review publication of the Radiological Society of North America, Inc. 35 (3): 680-95. doi:10.1148/rg.2015140110 - Pubmed
- 10. Rafeeq MM, Murad HAS. Cystic fibrosis: current therapeutic targets and future approaches. (2017) Journal of translational medicine. 15 (1): 84. doi:10.1186/s12967-017-1193-9 - Pubmed
- 11. Blau H, Blau FE, Blau MH, et al. Urogenital abnormalities in male children with cystic fibrosis. (2002) Archives of disease in childhood. doi:10.1136/adc.87.2.135 - Pubmed
- 12. Ong T & Ramsey B. Cystic Fibrosis: A Review. JAMA. 2023;329(21):1859-71. doi:10.1001/jama.2023.8120 - Pubmed
- 13. Shteinberg M, Haq I, Polineni D, Davies J. Cystic Fibrosis. Lancet. 2021;397(10290):2195-211. doi:10.1016/s0140-6736(20)32542-3 - Pubmed