Recommendations for research

1 Liver disease

Should all children with meconium ileus receive ursodeoxycholic acid from diagnosis?

Why this is important

Liver disease is the third most common cause of mortality in people with cystic fibrosis, and around 10 to 30% of people with cystic fibrosis will develop cystic-fibrosis-related liver disease. Children with meconium ileus are at an increased risk of liver disease, and starting treatment with ursodeoxycholic acid from diagnosis may reduce this risk. Ursodeoxycholic acid appears safe, is well tolerated and cheap. Routine use could increase people's overall quality of life and reduce the need for subsequent treatment for liver disease, but more research is needed into the effectiveness and safety of this treatment.

2 Airway clearance techniques

How effective are daily airway clearance techniques in maintaining lung function in infants and children with cystic fibrosis?

Why this is important

There has been debate about the level of physiotherapy needed to preserve lung health since healthcare systems started diagnosing cystic fibrosis through newborn screening. Some clinical teams teach parents airway clearance techniques and recommend using them daily, but others use alternatives such as parental respiratory assessment tools with structured exercise. Routine airway clearance from diagnosis takes up a lot of time and places considerable responsibility on the parents and carers. These techniques are also difficult to perform, particularly with an infant or young child who does not understand what is happening. It is important to find out whether daily airway clearance techniques are helping to maintain lung health or are creating an unnecessary burden on parents and carers. Future research should look at the impact on the lives of parents, family members and carers, as well as long-term clinical outcomes for infants and children with cystic fibrosis.

3 Monitoring pulmonary disease

Is lung clearance index a useful and cost-effective tool for the routine assessment and monitoring of changes in pulmonary status in people with cystic fibrosis?

Why this is important

Assessing the severity of lung disease is difficult in younger children. Not all children under 5 years can do spirometry tests and they are not sufficiently sensitive in people with good lung function, where CT scans can show pulmonary status changes before spirometry changes. A simple, sensitive and reproducible measurement such as lung clearance index allows assessment of respiratory status in people with cystic fibrosis, and could improve clinical decision-making.

4 Psychological assessment

What is the most effective measure of psychological functioning to use as a test for thresholds of concern in people with cystic fibrosis?

Why this is important

There are no validated tools to assess psychological and behavioural problems in people with cystic fibrosis, and these would be useful to validate generic measures (for example for depression and anxiety). People with a long-term physical health condition are more likely to present with mental health problems. NHS England highlights that prevention of mental health problems is the most cost-effective service that can be provided. To prevent mental health problems, all people with cystic fibrosis would need to have their mental health status routinely and regularly assessed. People with cystic fibrosis would benefit, therefore, from having a routine test that would show who needs psychological intervention. This would allow early intervention to maintain or improve quality of life, prevent mental health problems from developing, and improve health outcomes through an improvement in wellbeing.

What is the most effective strategy to detect diabetes in people with cystic fibrosis?

Why this is important

Diabetes develops and presents very differently in people with cystic fibrosis. Although annual testing for cystic-fibrosis-related diabetes is recommended in this guideline for people over 10 with cystic fibrosis, there is a lack of evidence on how to diagnose the condition. There is currently variation in practice, with cystic fibrosis centres using different combinations of the oral glucose tolerance test, HbA1c, serial glucose testing, and continuous glucose monitoring systems. Identifying which strategy is most effective for early identification of cystic-fibrosis-related diabetes would help teams start prompt treatment and prevent the clinical decline associated with the condition.

6 Mucoactive agents

What is the most clinically and cost-effective dose of rhDNase (dornase alfa; recombinant human deoxyribonuclease) for people with cystic fibrosis?

Why this is important

People with cystic fibrosis often have complex treatment schedules, which can include multiple nebulised treatments. Taking daily rhDNase increases the burden on them. Because of this, it is essential to find out whether rhDNase needs to be taken this often to provide clinical benefit. There is some evidence that alternate-day rhDNase is just as effective, and if this is confirmed then overall treatment adherence may improve and cost savings would be made. The current evidence base is mostly small, underpowered, short-term trials, in people who have had this treatment before. Consequently, it is not clear what the long-term impact of different doses of rhDNase are for people with cystic fibrosis. It may be cost effective to switch to alternate-day rhDNase if it is shown to be as effective as daily rhDNase.

Cystic fibrosis: diagnosis and management

Guidance