Cystic Fibrosis
CFTR modulators, airway clearance, PERT, and comprehensive CF management
Cystic fibrosis is a serious inherited condition that causes thick, sticky mucus to build up in the lungs, digestive system, and other organs. It is caused by mutations in the CFTR gene and affects around 10,500 people in the UK. Treatment has been transformed in recent years by CFTR modulator medicines — but management remains complex and lifelong, requiring input from a specialist multidisciplinary team.
What is Cystic Fibrosis?
Cystic fibrosis (CF) is an autosomal recessive genetic condition — meaning a person must inherit a faulty copy of the CFTR gene from both parents to develop the condition. The CFTR gene controls the movement of salt and water in and out of cells. When it is faulty, the mucus produced becomes abnormally thick and sticky, causing problems in the lungs, pancreas, liver, intestines, and reproductive system. In the UK, CF is diagnosed through the newborn bloodspot screening programme. The sweat test — measuring the concentration of chloride in sweat — is the main confirmatory test. A sweat chloride above 60 mmol/L is diagnostic.
Symptoms and Complications
The most significant effects of CF are in the lungs and digestive system. In the lungs, thick mucus traps bacteria and causes repeated infections, progressively damaging lung tissue. Pseudomonas aeruginosa is the most important chronic lung pathogen in CF, and once established, it cannot usually be eradicated. In the pancreas, blocked ducts prevent digestive enzymes from reaching the gut, causing malabsorption and poor growth — around 85% of people with CF need to take pancreatic enzyme supplements with all food. CF-related diabetes develops in around 20% of adults and requires insulin treatment. CF can also affect the liver, bones, sinuses, and fertility.
CFTR Modulator Medicines
The most significant advance in CF treatment has been the development of CFTR modulators — medicines that target the underlying protein defect rather than just managing symptoms. The combination of elexacaftor, tezacaftor, and ivacaftor (brand names Kaftrio and Kalydeco) is now recommended by NICE (TA830) for most people with CF aged 2 and over who have at least one copy of the F508del mutation — the most common mutation, present in around 90% of people with CF in the UK. These medicines have dramatically improved lung function, reduced hospitalisations, improved nutrition, and transformed quality of life for many patients. They must be taken with fat-containing food to ensure adequate absorption, and grapefruit juice and St John's Wort must be avoided.
Daily Management
Despite the benefits of modulators, daily management of CF remains intensive. Airway clearance physiotherapy — typically twice a day — helps loosen and clear mucus from the lungs. Nebulised medicines including dornase alfa and hypertonic saline are used to make mucus easier to clear. Pancreatic enzyme replacement therapy (PERT) must be taken immediately before or during every meal and snack to allow food to be properly digested. Fat-soluble vitamins A, D, E, and K need to be supplemented daily because they are not properly absorbed from food. Annual influenza vaccination is recommended. People with CF should not spend time with other CF patients due to the serious risk of cross-infection with harmful bacteria.
Long-Term Outlook
With current treatments including CFTR modulators, the outlook for people born with CF today is significantly better than for previous generations. The median predicted survival has improved considerably, and many people with CF now live into their forties, fifties, and beyond. However, CF remains a life-limiting condition for most. Regular review at an accredited CF centre is essential — annual assessments cover lung function, nutrition, diabetes screening, bone health, and mental wellbeing. For patients whose lung function declines severely, lung transplantation is an option that can significantly improve survival and quality of life.