Cystic fibrosis (CF) is a genetic condition. It is usually caused by a mutation in the CF transmembrane conductance regulator (CFTR) gene, called the F508del mutation. This causes the loss of phenylalanine at position 508 in the CFTR protein. There are about 9,500 people with CF in England and Wales, around 90% of whom have the F508del mutation. Impaired function of the CFTR protein affects salt and fluid transport. This causes a build-up of thick mucus in the lungs, the digestive system and the tubes that transport enzymes out of the pancreas. Before CFTR modulators were available, people with CF experienced a wide range of challenging symptoms affecting the whole body. Patient submissions explained how the build-up of thick mucus in the lungs leads to difficulty breathing, inflammation and severe infections that require hospitalisation for intravenous antibiotics. Bacteria can also colonise the lungs, leading to inflammation, tissue damage, repeated infections and permanent scarring. People with CF experience progressive lung function loss and are particularly vulnerable to antimicrobial resistance. Pancreatic enzyme supplements are needed to help digest food. Not taking these causes abdominal pain, bloating, excess wind, and difficulty gaining weight. Scarring of the pancreas can lead to CF-related diabetes. CF significantly shortens people's lives, with a median age of death in 2021 of 38 years. CF substantially impacts people's mental and emotional wellbeing and can have a large financial burden. Patient submissions also described the substantial impact on carers, due to the chronic and severe nature of CF. Caring for someone with CF is physically demanding and involves daily activities such as manual physiotherapy, administration of medicines, sterilising medical equipment and facilitating hospital visits. Parents have also described the difficulty of ensuring their children are a healthy weight and managing the high-calorie diet required. As well as being physically demanding, caring for someone with CF has a psychological and financial impact. Many carers experience anxiety, depression and fear about the future. Poor mental health can lead to physical health problems. Carers also report decreases in productivity, ability to work and job satisfaction. Because CF is a lifelong condition, carers can experience these effects over a long period of time. As well as impact on the primary caregiver, there is an impact on the whole family including siblings and grandparents. Patient experts at the committee meeting found it difficult and distressing to think back to a world before CFTR modulators, having experienced their transformative effects. One patient expert described the constant anxiety, depression and long-term pessimism of caring for a child with a terminal illness. Another patient expert described how life with CF was severely curtailed and the considerable mental toll of living with the condition. The committee acknowledged the substantial difficulties faced by people with CF. It recognised that CF is a chronic and severe condition that affects the body across multiple organ systems, can impact the mental wellbeing of people with the condition and their carers. It also acknowledged that CF is associated with considerable morbidity and can substantially shorten the lives of people with the condition.