What is cystic fibrosis and how is it treated?
Cystic fibrosis (CF) is an inherited disorder causing lung disease (bronchiectasis with persistent airway-based infection and inflammation), exocrine pancreatic insufficiency causing nutrient malabsorption and undernutrition, impaired growth, hepatobiliary disorders and male infertility [1]. It is caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which results in a dysfunctional chloride channel that disrupts chloride secretion, sodium reabsorption and water transport. CFTR has a role in epithelial cells at multiple sites (airways, intestine, pancreas, kidney, sweat gland, and male reproductive tract). Its effects on sodium and bicarbonate secretion result in inadequate hydration of secretions and mucins, resulting in the sticky mucus that causes lung disease and malnutrition, the most apparent effects of the disorder.
Genetics
The CFTR gene mutation is inherited in an autosomal recessive pattern (meaning the gene mutation must be inherited from both parents). More than 2,000 CFTR gene mutations have been identified, categorised in classes depending on function (little or none, residual or minimal). The impact of CF therefore ranges from a severe, widespread and early onset disorder to an isolated anatomical abnormality such as congenital absence of the vas deferens. The severity of CF is also influenced by environmental factors and genes that modulate the impact of the gene mutation. Unlike haemophilia, there is no difference in the severity of CF between males and females and carriers of the CFTR gene mutation are not affected [1].
Epidemiology
The epidemiology of CF and haemophilia are similar (Table 1). The most striking difference is life expectancy. Cystic fibrosis was once only seen in children, who died young. Advances in management have raised the life expectancy of people born now to the mid-40s in the UK. Chief among these improvements has been screening for the gene mutation as part of the NHS newborn blood spot test. This enables the provision of early treatment and support for families.
Table 1. Epidemiology of haemophilia and cystic fibrosis
| Haemophilia | Cystic fibrosis | |
| UK population | Haemophilia A: 8,616; Haemophilia B: 1,914 [2]
UKHCDO register 2019/2020: Total: 10,530 (excludes other bleeding disorders that centres manage) [3] |
Approx 1:2000 live births
10,600 registered patients [ |
| Global prevalence | Haemophilia A: 24.6 per 100,000 males (severe 9.5); Haemophilia B: 5.0 per 100,00 males (severe 1.5)
Registered cases worldwide: approx. 200,000 [2] |
North America: 7.97 per 100,000; Europe: 7.37 per 100,000
Worldwide: 100,000 |
| Life expectancy | 1985 – 1999 (UK median) Haemophilia A (severe): 63 yrs; Haemophilia A (mild/moderate): 75 yrs (excluding HIV) [5]
2001 (Netherlands) Life expectancy at birth: 72 yrs (excluding HIV and hepatitis) [6] |
2019 (UK median age at death): 31 yrs; 2019 median predicted survival: 49 yrs [4,7] |
Management
Management of cystic fibrosis is guided by NHS England service specifications for adults [8] and children [9], a NICE clinical guideline published in 2017 [10] and a 2018 European consensus guideline [11]. Services are delivered by multidisciplinary teams (Table 2) based at regional Specialist Cystic Fibrosis Centres, providing support to general hospitals (e.g. via outreach clinics) and primary care (shared care). There are 26 adult and 29 children’s centres in the UK. Services were previously audited by a peer review programme carried out by the Cystic Fibrosis Trust [12]. It is now the responsibility of NHS England’s Quality Surveillance Programme [13].
People with cystic fibrosis should be reviewed regularly, initially weekly in the first 4 weeks of age, then monthly until one year, then decreasing to every 3–6 months for adults. The primary treatment done at home several times a day include airway clearance, exercise, nutritional support and drug therapy. Long term antibiotic therapy aims to suppress bacterial lung infection, supported by preventing cross-infection. The viscosity of mucus is reduced by treatment with nebulised Dornase alfa and hypertonic saline, and inhaled mannitol. Genetic specific modulators (potentiators and correctors) are becoming available.
Representation
People with cystic fibrosis and their families/carers in the UK are represented by the Cystic Fibrosis Trust (CFT, www.cysticfibrosis.org.uk). The CFT hosts the UK Cystic Fibrosis Registry, which is managed by an independent Steering Committee (which includes patient representation). Registry data are used for severity banding to aid specialist commissioning and payment by the NHS, parents/patients sign consent for their data to be used for research and pharmacovigilance. Reports are published annually and are publicly available. The various members of the CF multidisciplinary team are members of specific special interest groups which contribute to national standards and guideline writing, organise meetings, education and sharing experience.
Table 2. The cystic fibrosis multidisciplinary team [5]
| CF multidisciplinary team | With access to expertise in |
| Consultant paediatrician/adult physician | Specialist microbiology |
| Specialist paediatricians or adult physicians | Pulmonary physiology |
| Specialist nurses | Diabetes/endocrinology |
| Specialist physiotherapists | Gastroenterology |
| Specialist dietitians | Hepatology |
| Specialist pharmacists | Rheumatology |
| Specialist clinical psychologists | Psychiatry |
| Include or have access to social workers | Interventional radiology |
| Registry/database coordinators | Surgery (gastrointestinal, thoracic, and ear, nose and throat) |
| Secretaries | Obstetrics |
| Palliative care |
References
1. Bell SC, Mall MA, Gutierrez H, Macek M, Madge S, et al. The future of cystic fibrosis care: a global perspective. Lancet Respir Med. 2020 Jan;8(1):65-124. doi: 10.1016/S2213-2600(19)30337-6.
2. World Federation of Hemophilia, WFH Annual Global Survey 2019. http://www1.wfh.org/publications/files/pdf-1806.pdf
3. http://www.ukhcdo.org/wp-content/uploads/2021/03/UKHCDO-%20Annual-Report-2020-2019-20-Data_FINAL.pdf
4. UK Cystic Fibrosis Registry. Annual Data Report 2019. August 2020
5. Darby SC, Kan SW, Spooner RJ, et al. Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV. Blood. 2007 Aug 1;110(3):815-25.
6. Plug I, Van Der Bom JG, Peters M, et al. Mortality and causes of death in patients with hemophilia, 1992-2001: a prospective cohort study. J Thromb Haemost. 2006 Mar;4(3):510-6.
7. Turcios NL. Cystic Fibrosis Lung Disease: An Overview. Respir Care. 2020 Feb;65(2):233-251.
8. https://www.england.nhs.uk/wp-content/uploads/2018/08/Cystic-fibrosis-adult.pdf
9. https://www.england.nhs.uk/wp-content/uploads/2018/07/a01Sb-spec-cystic-fibrosis-child.pdf
10. NICE NG78. 2017 https://www.nice.org.uk/guidance/ng78
11. European Cystic Fibrosis Society Best Practice Guidelines: 2018 revision. J Cystic Fibrosis 2018;17:153–178
12. https://www.cysticfibrosis.org.uk/the-work-we-do/resources-for-cf-professionals/peer-reviews
13. https://www.qst.england.nhs.uk