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Cystic fibrosis
Also known as Cystic fibrosis (residual function) · Cystic fibrosis (minimal function)
This inherited disorder leads to progressive damage to various organs, particularly the lungs, and can cause significant health challenges. It is typically diagnosed in childhood and impacts individuals globally.
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Overview
Cystic fibrosis (CF) is a life-long genetic condition that affects several organs in the body, most notably the lungs and the digestive system. It causes the body to produce unusually thick, sticky mucus, which can block airways and ducts. This build-up of mucus can lead to persistent lung infections, breathing difficulties, and problems with digesting food [PMID:33676798].
CF is one of the most common inherited disorders in the UK. While it primarily affects people of European descent, it can occur in individuals from any ethnic background. Improvements in medical care mean that many people with CF now live well into adulthood, although the severity of the condition can vary greatly between individuals.
Symptoms & clinical features
The symptoms of cystic fibrosis can vary widely in type and severity, even among individuals with the same genetic changes. They often appear during infancy or early childhood, but some people may not be diagnosed until later in life. Common respiratory symptoms include a persistent cough that produces thick mucus, recurrent lung infections (such as pneumonia or bronchitis), wheezing, and shortness of breath.
Digestive symptoms are also very common due to mucus blocking the ducts of the pancreas. This prevents digestive enzymes from reaching the intestines, making it difficult for the body to break down and absorb nutrients from food. This can lead to poor weight gain, malnutrition, greasy and foul-smelling stools, and abdominal pain [PMID:33676798]. Other potential symptoms can include clubbing of the fingers and toes, nasal polyps, and male infertility.
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Affected organs
Cystic fibrosis predominantly affects organs that produce mucus, sweat, and digestive fluids. The lungs are significantly impacted, with thick mucus obstructing the airways, leading to chronic infections and progressive lung damage. Over time, this can result in reduced lung function and respiratory failure.
The pancreas is another key organ affected, as thick mucus blocks the ducts that carry digestive enzymes to the small intestine. This impairs digestion and nutrient absorption. The liver can also be affected, potentially leading to liver disease, and the sweat glands produce sweat with a higher salt content, which is a key diagnostic indicator. In males, the tubes that carry sperm can be blocked or missing, leading to infertility in many cases [PMID:30129215].
Risks & severity
The severity of cystic fibrosis varies considerably. Some individuals experience mild symptoms, while others face severe, life-threatening complications. The condition is progressive, meaning symptoms can worsen over time, particularly lung damage. The lifetime risks associated with CF include chronic respiratory failure, severe malnutrition, CF-related diabetes, and liver disease.
Historically, the prognosis for individuals with CF was poor, but significant advancements in treatment have dramatically improved life expectancy and quality of life. The average life expectancy for individuals with CF has increased substantially over recent decades, with many now living into their 50s and beyond, particularly in high-income countries like the UK. Early diagnosis and consistent management are crucial for improving outcomes.
Genetic causes
Cystic fibrosis is caused by pathogenic variants in the CFTR gene. This gene provides instructions for making the Cystic Fibrosis Transmembrane Conductance Regulator protein. The CFTR protein acts as a channel across the membranes of cells, particularly those lining the lungs, pancreas, and other organs, to regulate the flow of chloride ions.
The movement of chloride ions is critical for controlling the movement of water in tissues, which in turn affects the consistency of mucus and other fluid secretions. Pathogenic variants in CFTR lead to a dysfunctional or absent CFTR protein. When the CFTR protein does not work correctly, chloride ions cannot move properly, causing water imbalance and resulting in thick, sticky mucus rather than thin, slippery secretions. This abnormal mucus then blocks ducts and airways, leading to the characteristic symptoms of CF [PMID:30129215]. There are many different types of pathogenic variants in the CFTR gene, and these can influence the specific symptoms and severity of CF.
- CFTR CF transmembrane conductance regulatorThe CFTR gene provides instructions for the CFTR protein, a chloride channel crucial for maintaining fluid balance and the production of thin, free-flowing mucus in various bodily systems.
Inheritance pattern
Cystic fibrosis is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of a pathogenic variant in the CFTR gene - one from each parent - to develop the condition. If a person inherits only one pathogenic variant copy, they are considered a 'carrier' of CF but typically do not experience symptoms themselves.
When both parents are carriers of a CFTR pathogenic variant, there is a 25% chance with each pregnancy that their child will inherit two copies of the variant and develop CF. There is a 50% chance the child will be a carrier like their parents, and a 25% chance the child will inherit no pathogenic variants and will not be a carrier. Family members of someone with CF or carriers may consider genetic counselling to understand their own risks and options for testing.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Subtypes & variants
This page covers Cystic fibrosis as a single condition. Several distinct variants and clinical subtypes are recognised in the literature - they share the underlying biology and broad management approach, but differ in severity, age of onset, or causative gene:
- Residual-function variants OMIM 219700
CFTR variants that retain partial protein activity. Typically associated with milder presentation, later diagnosis, and pancreatic sufficiency. Eligibility for some CFTR modulator therapies (such as ivacaftor) depends on this functional class.
- Minimal-function variants OMIM 219700
CFTR variants with little to no residual protein activity. Classic presentation with pancreatic insufficiency and progressive lung disease. Combination CFTR modulator therapy (elexacaftor/tezacaftor/ivacaftor) addresses minimal-function variants in eligible genotypes.
Diagnosis & testing
Diagnosis of cystic fibrosis in the UK often begins with newborn screening, which is offered to all babies through the NHS. This involves a 'heel prick' blood test, typically done shortly after birth. If the screening test suggests CF, further diagnostic tests are carried out. The primary confirmatory test is the 'sweat test', which measures the amount of salt in a person's sweat; individuals with CF typically have unusually high levels of chloride in their sweat [PMID:33676798].
Genetic testing, specifically looking for pathogenic variants in the CFTR gene, confirms the diagnosis and can also help determine the specific type of CF and inform treatment options. Genetic testing for CFTR is available through the NHS Genomic Medicine Service, often requested by a specialist clinician using R-codes such as R42 (Cystic fibrosis). Referral to a clinical geneticist or specialist paediatrician is usually made for further assessment and management.
Management & lifestyle
The management of cystic fibrosis is complex and multidisciplinary, focusing on controlling symptoms, preventing complications, and improving quality of life. There is no cure for CF, but treatments aim to manage the disease effectively. This typically involves a combination of therapies tailored to the individual's specific needs.
Regular respiratory physiotherapy is essential to clear mucus from the lungs, often alongside inhaled medications to open airways and antibiotics to treat infections. Dietary management, including enzyme supplements and nutritional advice, is crucial to address digestive issues and maintain healthy weight. Newer treatments, known as CFTR modulators, target the underlying protein defect and can significantly improve lung function and overall health for many individuals with specific CFTR pathogenic variants. Patients are typically managed through specialist CF centres within the NHS, ensuring access to a team of experts including doctors, nurses, physiotherapists, dietitians, and genetic counsellors [PMID:33676798].
Ongoing monitoring, including regular lung function tests and nutritional assessments, is a key part of the management plan. Lifestyle considerations, such as regular exercise and avoiding exposure to respiratory irritants, are also important.
UK care pathway
In the UK, the care pathway for cystic fibrosis is well-established through the NHS. Following a positive newborn screening or suspicion of CF, individuals are typically referred to specialist NHS CF Centres. These centres provide comprehensive, multidisciplinary care, aligning with the NHS Genomic Medicine Service (GMS) framework.
Genetic testing for CFTR pathogenic variants is available via the GMS, often requested by a specialist using an appropriate R-code, such as R42 (Cystic fibrosis). A referral to a clinical genetics service is an integral part of this pathway, offering genetic counselling to patients and their families to discuss inheritance patterns, reproductive options, and support networks.
Frequently asked questions
What is a 'carrier' of cystic fibrosis?
A carrier of cystic fibrosis has one copy of a pathogenic variant in the CFTR gene but does not typically show symptoms of the condition themselves. They can pass this variant on to their children. If both parents are carriers, there is a chance their child could develop CF.
How is cystic fibrosis usually diagnosed in the UK?
In the UK, cystic fibrosis is often first identified through newborn screening, which involves a heel prick test. If this screening is positive, a sweat test and genetic testing for CFTR pathogenic variants are usually performed to confirm the diagnosis.
Can cystic fibrosis be cured?
Currently, there is no cure for cystic fibrosis. However, significant advancements in treatment, including physiotherapy, medications, and CFTR modulators, help manage symptoms, prevent complications, and greatly improve the quality of life and life expectancy for individuals with CF.
How does cystic fibrosis affect daily life?
Cystic fibrosis requires ongoing daily management, including regular medications, physiotherapy sessions, and sometimes specific dietary requirements. This can significantly impact daily routines, but many individuals with CF lead full and active lives with proper care and support.
What should I do if I have a family history of cystic fibrosis?
If you have a family history of cystic fibrosis, it is advisable to speak with your GP or a genetic counsellor. They can provide information about carrier testing, discuss the inheritance patterns, and help you understand any potential risks for you and your family.
References
- Shaw JAM. Editorial: Cystic fibrosis-related diabetes. Frontiers in endocrinology. 2024. PMID: 39129918
- Schechter MS. Speaking of pandemics.. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2021. PMID: 34103249
- Karadag BT, Hatziagorou E, Teper A. Editorial: Cystic Fibrosis in Children. Frontiers in pediatrics. 2022. PMID: 35592838
- Sakiani S, Kleiner DE, Heller T. Hepatic Manifestations of Cystic Fibrosis. Clinics in liver disease. 2019. PMID: 30947876
- Savant AP, McColley SA. Cystic fibrosis year in review 2017. Pediatric pulmonology. 2018. PMID: 29927544
- Azithromycin and cystic fibrosis. Archives of disease in childhood. 2022. PMID: 35853636
- Solomon M, Bozic M, Mascarenhas MR. Nutritional Issues in Cystic Fibrosis. Clinics in chest medicine. 2016. PMID: 26857771
- Thornton T, Pillai A. Encephalopathy in cystic fibrosis. Paediatric respiratory reviews. 2020. PMID: 32800451