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Cystic fibrosis

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Cystic fibrosis article more useful, or one of our other health articles.

Cystic fibrosis (CF) is a multi-organ disease best managed in a multidisciplinary setting in conjunction with a specialist centre for CF, with treatment tailored to the individual.

Conventional treatment has improved greatly over the past few decades. Newer approaches such as gene and small molecule-based treatments may have more potential to halt disease progression.

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CF is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, on chromosome 71. There are at least 2,000 mutations in the CFTR gene. Different mutations result in different phenotypes. Some mutations result in milder forms of the disease. One study identified some mutations which appeared to have no pathological effect at all2. The most common mutation in Caucasians is the delta-F508 (DF508).

CFTR is an ATP-responsive chloride channel that also affects other cellular activities, such as sodium transport across the respiratory epithelium, composition of cell surface glycoprotein and antibacterial defences.


CF is the most common inherited disease in white populations3.

  • Prevalence in Caucasians is 1 in 3,000-4,000 newborn infants4, with calculated carrier frequency of 1 in 255. 10,509 people were recorded as having CF in the 2018 UK CF Registry6.

  • The only risk factor is a family history of the condition.

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The abnormality in the CFTR gene explains the pathology of CF.

High sodium sweat

Primary secretion of sweat duct is normal but CFTR does not absorb chloride ions, which remain in the lumen and prevent sodium absorption.

Pancreatic insufficiency

Production of pancreatic enzymes is normal but defects in ion transport produce relative dehydration of pancreatic secretions, causing their stagnation in the pancreatic ducts.

Biliary disease

Defective ion transfer across the bile duct causes reduced movement of water in the lumen so that bile becomes concentrated, causing plugging and local damage.

Gastrointestinal disease

Low-volume secretions of increased viscosity, changes in fluid movement across both the small and large intestine and dehydrated biliary and pancreatic secretions cause intraluminal water deficiency.

Respiratory disease

Dehydration of the airway surfaces reduces mucociliary clearance and favours bacterial colonisation; local bacterial defences are impaired by local salt concentrations and bacterial adherence is increased by changes in cell surface glycoproteins.

Increased bacterial colonisation and reduced clearance produce inflammatory lung damage due to an exuberant neutrophilic response involving mediators such as IL8 and neutrophil elastase.


  • As normal digestive function is possible with <5% pancreatic function, CF can present at any age.

  • The most common presentation is with respiratory problems - usually recurrent lower respiratory tract infection (LRTI) with chronic sputum production.

However, immunoreactive trypsinogen (IRT) is now measured on a dried blood spot obtained on the Guthrie card at day six of life. Samples with abnormally raised IRT levels will undergo CFTR mutation screening. This was introduced in 2007. This therefore means that clinical presentation of CF will become rarer. However, screening failures do sometimes occur. Presentation of CF varies with age.

Presentation and diagnosis7


Amniocentesis/chorionic villus sampling (CVS).

Ultrasound demonstration of bowel perforation/hyperechogenic bowel (4% cases due to CF).



Bowel obstruction with meconium ileus (bowel atresia).

Haemorrhagic disease of the newborn.

Prolonged jaundice.

Infancy and childhood

Family history.

Recurrent respiratory infections.

Chronic pulmonary disease.


Failure to thrive (thriving does not exclude diagnosis).

Rectal prolapse.

Nasal polyps (in children, nearly always due to CF).

Acute pancreatitis.

Portal hypertension and variceal haemorrhage.

Pseudo-Bartter's syndrome, electrolyte abnormality.

Hypoproteinaemia and oedema.



Family history.

Recurrent respiratory infections.

Atypical asthma.


Chronic pulmonary disease.

Chronic sinus disease.

Male infertility with congenital bilateral absence of the vas deferens.

Heat exhaustion/electrolyte disturbance.

Portal hypertension and variceal haemorrhage.


These may include:

  • Finger clubbing.

  • Cough with purulent sputum.

  • Crackles.

  • Wheezes (mainly in the upper lobes).

  • Forced expiratory volume in one second (FEV1) showing obstruction.

Babies diagnosed with CF will usually have no signs or symptoms.

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  • Sweat testing confirms the diagnosis and is 98% sensitive. Chloride concentration >60 mmol/L with sodium concentration lower than that of chloride on two separate occasions.

  • Molecular genetic testing for CFTR gene.

  • Sinus X-ray or CT scan - opacification of the sinuses is present in almost all patients with CF.

  • CXR or CT of thorax.

  • Lung function testing - spirometry is unreliable before 6 years.

  • Sputum microbiology - common pathogens include Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, Escherichia coli and Klebsiella pneumoniae.

  • Various blood tests including FBC, U&Es, fasting glucose, LFTs and vitamin A, D and E levels are usually performed.

  • Semen analysis if appropriate.


Most patients' care is co-ordinated by a CF tertiary centre9. However, an Australian study found no difference in care between that provided in specialist centres and that provided by outreach services. This may be more relevant in remote areas10. A German study reported that CF patients most valued healthcare staff who were friendly, approachable and communicative11.

Respiratory problems

Most of the morbidity and mortality associated with CF is caused by respiratory disease where chronic infection and inflammation lead to bronchiectasis, progressive airflow obstruction, cor pulmonale and finally death.

Probably as a result of more successful treatment of classic bacterial infections in CF, there are now increasing problems with multi-resistant isolates of P. aeruginosa and innately resistant organisms such as Stenotrophomonas maltophilia, Achromobacter xylosoxidans and non-tuberculous mycobacteria. Meticillin-resistant S. aureus (MRSA) is a growing problem.

The following interventions are commonly used to prevent and treat 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 and this is increased with infective exacerbations.

  • Additional physical exercise is also beneficial and should be encouraged.

  • Regular sputum samples are sent for bacterial culture.

  • Prophylactic antibiotics are used to reduce S. aureus in children and also to prevent secondary bacterial infections when a patient has a presumed acute viral respiratory infection.

  • Antibiotic choice for infective exacerbations will depend on the organism.

  • Infection with less common organisms requires specialist microbiological advice.

  • Patients with P. aeruginosa have a 2- to 3-fold increased risk of death over eight years. This is eradicated by various combinations of oral, inhaled and intravenous antibiotics. Pre-colonisation pseudomonal eradication protocols usually include both topical (nebulised) and systemic antibiotics. A Cochrane review looking at various combinations of oral ciprofloxacin, inhaled colistin and nebulised tobramycin solution failed to show superiority of any particular regime12. Intravenous home treatment using tobramycin and amikacin is often used where suitably trained staff are available.

  • The National Institute for Health and Care Excellence (NICE) recommends treatment of chronic P. aeruginosa with nebulised colistimethate sodium or tobramycin. For patients who cannot take the nebulised form, NICE has recommended dry powder inhalation formulations of these drugs13.

  • A Cochrane review found insufficient evidence to suggest a significant beneficial effect on FEV1 by inhaled bronchodilators and recommended further research into spirometric changes from baseline, quality of life and adverse effects14.

  • Dornase alfa is a recombinant form of human deoxyribonuclease and is given by nebuliser. It cleaves neutrophil-derived DNA in sputum to reduce viscosity and therefore aid sputum removal. It has been shown to be associated with improvement in lung function and possibly a reduction in respiratory exacerbations. Cochrane looked at the timing of administration before and after airway clearance and found no difference in adults. The results in children were equivocal and required further research15.

  • High-dose ibuprofen may slow progression of lung disease, especially in children.

  • Azithromycin has also been shown to reduce inflammation and improve respiratory function in CF. However, benefits beyond six months and the issue of emerging resistance require further research16.

  • Hypertonic saline by a nebuliser is often given for its osmotic action. Other osmotic agents are being developed. A Cochrane review found poor-quality evidence and concluded that further research was required to identify the subtypes of patients who would most benefit from this type of treatment17.

  • Mannitol dry powder for inhalation is recommended by NICE as an option for treating cystic fibrosis in adults18:

    • Who cannot use rhDNase because of ineligibility, intolerance or inadequate response to rhDNase; and

    • Whose lung function is rapidly declining (FEV1 decline greater than 2% annually); and

    • For whom other osmotic agents are not considered appropriate.

  • A Cochrane review could not obtain sufficient high-quality evidence to conclude whether inhaled corticosteroids were beneficial in cystic fibrosis19.

  • In the end stage, management focuses on the common complications, which include haemoptysis, pneumothorax and respiratory failure.

  • Lung or heart and lung transplantation listing should be considered where there is respiratory failure. Due to scarcity of donor organs, approximately a third of CF patients on the list die before receiving a donor lung20. It is hoped that the new technique of ex vivo lung perfusion will help to increase the stock of lungs available21.

Nasal polyps

50% of adults with CF have nasal polyps. Treat with nasal steroids initially; if this fails, polypectomy is usually performed (50% require repeat within two years).

Pancreatic insufficiency

At least 85% of patients with CF have pancreatic insufficiency..This usually presents with neonatal meconium ileus or failure to thrive, steatorrhoea and malnutrition which can cause anaemia, vitamin deficiency and sometimes oedema. It can cause rectal prolapse, intussusception, volvulus and obstruction.

Pancreatic insufficiency should be confirmed with stool elastase; presence of unsplit fat globules in stool or 2-3 days' stool collection for faecal fat.

Pancreatic enzymes are traditionally prescribed. However, a Cochrane review has found that there is no evidence regarding the risks and benefits of long-term treatment, nor on the timing of doses22.

Maintaining adequate weight

Patients should be weighed regularly. They will have high energy needs, especially those with recurrent chest infections or those who lose a lot of fat in their stools. Protein intake needs to be at least twice the normal recommended amounts.

  • Despite the issues evident in the Cochrane review above, the British National Formulary recommends taking enteric-coated enzyme preparations with, immediately before or just after food to achieve optimal concentration in the duodenum.The dose is adjusted to achieve normal stools. Drugs may be needed to reduce acid secretion, as well as vitamin supplements for the fat-soluble vitamins A, D and E.

  • High intake of calories (130% normal) is usually required23.

    • Comparing actual resting energy expenditure (REE) to predicted REE is an objective indicator of disease severity and progression as well as energy requirements. There is evidence of a recent trend for patients to exceed their energy requirements and develop obesity. The REE approach is helpful in understanding this phenomenon24.

    • Research supports the use of high-calorie diets in underweight patients but further work needs to be done on the most efficacious route of delivery.

    • If the patient is unable to maintain weight, enteral feeding via gastrostomy may be required.

    • There is no evidence that oral calorie supplements are beneficial for children with CF. Short-term protein supplements may be of benefit in adults but further research is required25.

Liver disease26

Liver disease is seen in up to 30% of patients by adulthood. Liver cell failure usually occurs late, with ominous prognosis. It is fatal in 2-4% of CF cases and is the third most common cause of death in CF patients.

  • Commonly, LFTs are abnormal and should be treated with caution. They can be a reflection of CF without liver disease, CF-related liver disease or the side-effects of medication27.

  • Usually seen as hepatosplenomegaly.

  • Ultrasound is a useful confirmatory investigation. Other imaging modes - eg, scintigraphy - may be required.

  • Ursodeoxycholic acid improves bile flow and produces some improvement but does not alter the course of chronic liver disease.

Liver transplantation should be offered to CF patients with progressive liver failure and/or with life-threatening sequelae of portal hypertension. They should also have relatively good lung function, to support long-term survival.

Diabetes and glucose intolerance

A 2014 Danish study reported an incidence of CF-related diabetes among 11- to 16-year-old children of 12-14%, This incidence remained unchanged over the previous two decades28.

  • Screening for diabetes is performed at regular intervals.

  • Insulin replacement is usually required with the dose adjusted to match high dietary intake. Early insulin therapy may be beneficial but further research is required29.

  • A Cochrane review found no significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycaemic agents had a distinct advantage over one another in controlling hyperglycaemia or clinical outcomes associated with CF-related diabetes30.

Reproductive health and fertility

Nearly all males with CF have obstructive azoospermia with sexual function that is otherwise normal; there is normal spermatogenesis but no vas deferens. Early counselling should be offered about infertility and sperm count. In vitro fertilisation with aspirated sperm has been used successfully.

Women are generally of normal fertility but need genetic counselling. There is an inherent risk to pregnancy with severe lung disease (FEV1 <30% predicted).

Offspring of patients with CF will be carriers of cystic fibrosis.

Psychological problems

CF is a huge burden to patients and families. This is because of:

  • The life-shortening nature of the disease.

  • The time-consuming treatments prescribed.

  • The ongoing morbidity.

Insufficient evidence exists on psychological interventions or approaches to support people with CF and their caregivers and multicentre studies are needed31.


There is an increased risk of osteoporosis in patients with CF. Around one third of adults with CF have osteoporosis.

Patients should be recommended to take calcium, vitamin D and bisphosphonates as appropriate. Patients usually have regular dual-energy X-ray absorptiometry (DXA) scans.

Follow-up of patients8

Patients have regular follow-up by their specialist.

UK standards recommend that:

  • Patients should be seen twice a year by a multidisciplinary team working in a specialist centre.

  • GPs should provide shared care in conjunction with specialists.

  • Children should be transferred to adult services by the age of 18 at the latest.

In general, the following investigations are performed at regular intervals:

  • Pulmonary function tests.

  • CXR.

  • DXA scan.

  • Blood glucose.

  • Respiratory cultures.

  • Ultrasound scan of the liver.

  • Vitamin D levels.

Varicella antibodies are usually checked for and the varicella vaccine is usually offered to those children who need it.

All patients should receive the annual influenza vaccination. They should also receive the pneumococcal vaccine.


The pronounced improvement in life expectancy over the period of two decades is largely the result of centralisation of care at CF centres and aggressive treatment of symptoms.

  • Median survival in 1999 was 30 years. Projected life expectancy for patients increased from 31 years to 37 years over the period of a decade33.

  • A UK longitudinal study reported an estimated survival of 45-57 in males (depending on age of diagnosis) and 40 in females34.

  • Females and those people of lower socio-economic status have a worse prognosis35.

  • The use of rDNase has been shown to lead to a marked improvement in survival of patients with a low FEV136.

The future

The great hope for the future is that therapies that treat the basic defect will normalise life expectancy for those born with CFTR mutations. One study of liposome-based CFTR gene transfer therapy demonstrated some improvements in respiratory function in people with CF. However, more research is needed37

Further reading and references

  • Farrell PM, Rock MJ, Baker MW; The Impact of the CFTR Gene Discovery on Cystic Fibrosis Diagnosis, Counseling, and Preventive Therapy. Genes (Basel). 2020 Apr 8;11(4). pii: genes11040401. doi: 10.3390/genes11040401.
  • Kulkarni H, Kansra S, Karande S; Cystic fibrosis revisited. J Postgrad Med. 2019 Oct-Dec;65(4):193-196. doi: 10.4103/jpgm.JPGM_263_18.
  1. Cystic Fibrosis, CF; Online Mendelian Inheritance in Man (OMIM)
  2. Sosnay PR, Siklosi KR, Van Goor F, et al; Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013 Oct;45(10):1160-7. doi: 10.1038/ng.2745. Epub 2013 Aug 25.
  3. Davies JC, Alton EW, Bush A; Cystic fibrosis. BMJ. 2007 Dec 15;335(7632):1255-9.
  4. Sanders DB, Fink AK; Background and Epidemiology. Pediatr Clin North Am. 2016 Aug;63(4):567-84. doi: 10.1016/j.pcl.2016.04.001.
  5. Ratjen F, Doring G; Cystic fibrosis. Lancet. 2003 Feb 22;361(9358):681-9.
  6. UK CF Registry at-a-glance report; Cystic Fibrosis Trust, 2018
  7. Cystic fibrosis: diagnosis and management; NICE Guideline (Oct 2017)
  8. Standards for the Clinical Care of Children and Adults with cystic fibrosis in the UK; Cystic Fibrosis Trust, December 2011, updated 2013 Link to pdf file.
  9. Conway S, Balfour-Lynn IM, De Rijcke K, et al; European Cystic Fibrosis Society Standards of Care: Framework for the Cystic Fibrosis Centre. J Cyst Fibros. 2014 May;13 Suppl 1:S3-22. doi: 10.1016/j.jcf.2014.03.009.
  10. Weber HC, Robinson PF, Saxby N, et al; Do children with cystic fibrosis receiving outreach care have poorer clinical outcomes than those treated at a specialist cystic fibrosis centre? Aust J Rural Health. 2017 Feb;25(1):34-41. doi: 10.1111/ajr.12334. Epub 2016 Nov 17.
  11. Steinkamp G, Stahl K, Ellemunter H, et al; Cystic fibrosis (CF) care through the patients' eyes - a nationwide survey on experience and satisfaction with services using a disease-specific questionnaire. Respir Med. 2015 Jan;109(1):79-87. doi: 10.1016/j.rmed.2014.11.007. Epub 2014 Dec 6.
  12. Langton Hewer SC, Smyth AR; Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev. 2017 Apr 25;4:CD004197. doi: 10.1002/14651858.CD004197.pub5.
  13. Colistimethate sodium and tobramycin dry powders for inhalation for treating pseudomonas lung infection in cystic fibrosis; NICE Technology appraisal guidance, March 2013
  14. Smith S, Edwards CT; Long-acting inhaled bronchodilators for cystic fibrosis. Cochrane Database Syst Rev. 2017 Dec 19;12:CD012102. doi: 10.1002/14651858.CD012102.pub2.
  15. Dentice R, Elkins M; Timing of dornase alfa inhalation for cystic fibrosis. Cochrane Database Syst Rev. 2018 Nov 12;11:CD007923. doi: 10.1002/14651858.CD007923.pub5.
  16. Southern KW, Barker PM, Solis-Moya A, et al; Macrolide antibiotics for cystic fibrosis. Cochrane Database Syst Rev. 2012 Nov 14;11:CD002203. doi: 10.1002/14651858.CD002203.pub4.
  17. Wark P, McDonald VM; Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2018 Sep 27;9:CD001506. doi: 10.1002/14651858.CD001506.pub4.
  18. Mannitol dry powder for inhalation for treating cystic fibrosis; NICE Technology Appraisal Guidance, November 2012
  19. Balfour-Lynn IM, Welch K, Smith S; Inhaled corticosteroids for cystic fibrosis. Cochrane Database Syst Rev. 2019 Jul 4;7:CD001915. doi: 10.1002/14651858.CD001915.pub6.
  20. Transplants in cystic fibrosis; Cystic Fibrosis Trust
  21. Machuca TN, Cypel M; Ex vivo lung perfusion. J Thorac Dis. 2014 Aug;6(8):1054-62. doi: 10.3978/j.issn.2072-1439.2014.07.12.
  22. Somaraju UR, Solis-Moya A; Pancreatic enzyme replacement therapy for people with cystic fibrosis. Cochrane Database Syst Rev. 2016 Nov 23;11:CD008227. doi: 10.1002/14651858.CD008227.pub3.
  23. Kaplan A et al; Medical Issues And The Eating Disorders: The Interface, 2013.
  24. Litvin M, Yoon JC, Leey Casella J, et al; Energy balance and obesity in individuals with cystic fibrosis. J Cyst Fibros. 2019 Oct;18 Suppl 2:S38-S47. doi: 10.1016/j.jcf.2019.08.015.
  25. Smyth RL, Rayner O; Oral calorie supplements for cystic fibrosis. Cochrane Database Syst Rev. 2017 May 4;5:CD000406. doi: 10.1002/14651858.CD000406.pub5.
  26. Kobelska-Dubiel N, Klincewicz B, Cichy W; Liver disease in cystic fibrosis. Prz Gastroenterol. 2014;9(3):136-41. doi: 10.5114/pg.2014.43574. Epub 2014 Jun 26.
  27. Mayer-Hamblett N, Kloster M, Ramsey BW, et al; Incidence and clinical significance of elevated liver function tests in cystic fibrosis clinical trials. Contemp Clin Trials. 2013 Mar;34(2):232-8. doi: 10.1016/j.cct.2012.11.005. Epub 2012 Nov 29.
  28. Knudsen KB, Mathiesen ER, Eriksen V, et al; The development of diabetes among Danish cystic fibrosis patients over the last two decades. Pediatr Diabetes. 2015 May;16(3):219-26. doi: 10.1111/pedi.12143. Epub 2014 Jun 1.
  29. Hameed S, Jaffe A, Verge CF; Cystic fibrosis related diabetes (CFRD)--the end stage of progressive insulin deficiency. Pediatr Pulmonol. 2011 Aug;46(8):747-60. doi: 10.1002/ppul.21495. Epub 2011 May 27.
  30. Onady GM, Stolfi A; Insulin and oral agents for managing cystic fibrosis-related diabetes. Cochrane Database Syst Rev. 2013 Jul 26;7:CD004730. doi: 10.1002/14651858.CD004730.pub3.
  31. Goldbeck L, Fidika A, Herle M, et al; Psychological interventions for individuals with cystic fibrosis and their families. Cochrane Database Syst Rev. 2014 Jun 18;6:CD003148. doi: 10.1002/14651858.CD003148.pub3.
  32. Conwell LS, Chang AB; Bisphosphonates for osteoporosis in people with cystic fibrosis. Cochrane Database Syst Rev. 2014 Mar 14;3:CD002010. doi: 10.1002/14651858.CD002010.pub4.
  33. O'Sullivan BP, Freedman SD; Cystic fibrosis. Lancet. 2009 May 30;373(9678):1891-904. Epub 2009 May 4.
  34. Keogh RH, Szczesniak R, Taylor-Robinson D, et al; Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data. J Cyst Fibros. 2018 Mar;17(2):218-227. doi: 10.1016/j.jcf.2017.11.019. Epub 2018 Jan 6.
  35. Barr HL, Britton J, Smyth AR, et al; Association between socioeconomic status, sex, and age at death from cystic fibrosis in England and Wales (1959 to 2008): cross sectional study. BMJ. 2011 Aug 23;343:d4662. doi: 10.1136/bmj.d4662.
  36. Naehrig S, Chao CM, Naehrlich L; Cystic Fibrosis. Dtsch Arztebl Int. 2017 Aug 21;114(33-34):564-574. doi: 10.3238/arztebl.2017.0564.
  37. Lee TW, Southern KW, Perry LA, et al; Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease. Cochrane Database Syst Rev. 2016 Jun 17;(6):CD005599. doi: 10.1002/14651858.CD005599.pub5.

Article history

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