A.5.1. Who is the focus?

• Groups that will be covered
• Infants, children, young people and adults with cystic fibrosis, including those who have
• non-classic cystic fibrosis and those who have had an organ transplant.
• Groups that will not be covered

A.5.2. Settings

• Settings that will be covered
• all settings in which NHS-commissioned healthcare is provided.

A.5.3. Activities, services or aspects of care

• Key areas that will be covered
• The following clinical issues that will be covered in this guideline:
• The clinical manifestations of cystic fibrosis at the time of diagnosis in infants, children, young people and adults.
• The complications of cystic fibrosis
• Management of chest disease:
• Routine monitoring of lung disease, including microbiological surveillance, radiological imaging and pulmonary function testing.
• Antimicrobial management in cystic fibrosis to:

  • prevent bacterial colonisation
  • treat acute pulmonary infection
  • treat chronic pulmonary infection, including clinical exacerbations and colonisation.
• Immunomodulatory management in chest disease
• Management with mucoactive or mucolytic agents.
• Chest physiotherapy.
• The role of exercise in maintaining health.
• Management of nutrition.
• Management of exocrine pancreatic insufficiency.
• Management of distal intestinal obstruction syndrome.
• Surveillance for cystic-fibrosis-related diabetes.
• Surveillance for cystic-fibrosis-related liver disease and prevention of progression.
• Surveillance for reduced bone mineral density.
• Recognising psychological and behavioural problems.
• Models for delivery of care and multidisciplinary teams.
• Provision of information and support for infants, children, young people, adults and their carers

Note that guideline recommendations will normally fall within licensed indications. Exceptionally, and only if clearly supported by evidence, use outside a licensed indication may be recommended. This guideline will assume that prescribers will use a drug’s summary of product characteristics to inform decisions made with individual patients.

• Areas that will not be covered

This guideline does not cover:

• Specialist management of cystic-fibrosis-related diabetes.
• Specialist management of cystic-fibrosis-related fertility and pregnancy problems.
• Specialist management of cystic-fibrosis-related liver disease.
• Specialist management of cystic-fibrosis-related bone disease.
• Specialist management of cystic-fibrosis-related ear, nose and throat (ENT) disorders.
• Specialist management of cystic-fibrosis-related renal disease.
• Surgical management of gastrointestinal complications.
• Referral for, and management of, transplantation.
• Management of specific psychological conditions.
• Management of specific behavioural problems.

A.5.4. Economic aspects

We will take economic aspects into account when making recommendations. We will develop an economic plan that states for each review question (or key area in the scope) whether economic considerations are relevant, and if so whether this is an area that should be prioritised for economic modelling and analysis. We will review the economic evidence and carry out economic analyses, using an NHS perspective, as appropriate.

A.5.5. Key issues and questions

While writing this scope, we have identified the following key issues, and key questions related to them:

1. Diagnosis and complications

   • What are the clinical manifestations of cystic fibrosis at the time of diagnosis in infants, children, young people and adults?
   • What are the complications of cystic fibrosis?
2. Management of pulmonary disease

   • What is the effectiveness of the following in monitoring pulmonary disease?

     –

     Microbiological investigation, including techniques such as bronchoscopy and lavage

     –

     Chest X-ray

     –

     Chest computed tomography (CT) scan

     –

     Lung function testing, including lung clearance index and forced expiratory volume in 1 second (FEV1).

   • What is the effectiveness of antimicrobial treatment:

     –

     To prevent bacterial colonisation

     –

     To treat acute pulmonary infection

     –

     To treat chronic pulmonary infection, including clinical exacerbations and colonisation?

   • What is the effectiveness of mucoactive or mucolytic agents, including rhDNase, nebulised saline (isotonic and hypertonic) and mannitol?
   • What is the effectiveness of immunomodulatory agents in the management of lung disease (for example, corticosteroids, azithromycin)?
   • What is the effectiveness of airway clearance techniques in people with cystic fibrosis?
3. What is the effectiveness of exercise programmes in the management of cystic fibrosis?
4. Gastrointestinal manifestations

   • What is the effectiveness of enzyme replacement in the treatment of exocrine pancreatic insufficiency?
   • What are the effective strategies for prevention and treatment of distal ileal obstruction syndrome?
5. Nutritional care

   • What is the effectiveness of nutritional interventions in cystic fibrosis?
6. Cystic Fibrosis related diabetes

   • How should people with cystic fibrosis be monitored for the onset of cystic-fibrosis-related diabetes?
7. Liver disease

   • What is the effectiveness of ultrasound scanning to detect clinically important cysticfibrosis-related liver disease?
   • What is the effectiveness of ursodeoxycholic acid for preventing liver disease progression in people with cystic fibrosis?
8. Bone disease

   • How should monitoring be carried out to identify reduced bone mineral density?
9. Psychological and behavioural problems

   • How should people with cystic fibrosis be monitored for psychological or behavioural problems?
10. Information and support

    • What information and support should be offered to people with cystic fibrosis?
11. Delivery of care

    • What is the most effective model for delivery of care for people with cystic fibrosis (including multidisciplinary teams of varied compositions, shared care, centre care, community care, home care and telemedicine)?
    • How can services be organised to minimise the risk of cross-infection?
    • What parts of the transition from children’s to adult services are most important for young people with cystic fibrosis and their family members and carers?

A.5.6. Main outcomes

The main outcomes that will be considered when searching for and assessing the evidence are:

1. Health-related quality of life.
2. Height, weight and BMI.
3. Survival rates.
4. Lung function (for example, FEV1).
5. Rate of acute pulmonary infections, including those needing hospitalisation.
6. Prevalence of infection with specific bacterial pathogens.
7. Patient satisfaction.

A.6.1. NICE guidance

• Gastro-oesophageal reflux disease (2015) NICE guideline NG1
• Dyspepsia and gastro-oesophageal reflux disease (2014) NICE guideline CG184
• Infection: prevention and control of healthcare-associated infections in primary and community care (2012) NICE guideline CG139
• Constipation in children and young people (2010) NICE guideline CG99
• Depression in adults with a chronic physical health problem (2009) NICE guideline CG91
• Living-donor lung transplantation for end-stage lung disease (2006) NICE interventional procedure guidance 170

A.6.2. NICE guidance that will be updated by this guideline

Depending on the outcome of a NICE technology appraisal review proposal this guideline will either update and replace, or incorporate, the following NICE guidance:

• Colistimethate sodium and tobramycin dry powders for inhalation for treating pseudomonas lung infection in cystic fibrosis (2013) NICE technology appraisal guidance 276
• Mannitol dry powder for inhalation for treating cystic fibrosis (2012) NICE technology appraisal guidance 266
• NICE guidance about the experience of people using NHS services

NICE has produced the following guidance on the experience of people using the NHS. This guideline will not include additional recommendations on these topics unless there are specific issues related to cystic fibrosis:

• Patient experience in adult NHS services (2012) NICE guideline CG138
• Service user experience in adult mental health (2011) NICE guideline CG136
• Medicines adherence (2009) NICE guideline CG76

A.6.3. NICE Pathways

When this guideline is published, the recommendations will be added to NICE Pathways. NICE Pathways bring together all related NICE guidance and associated products on a topic in an interactive topic-based flow chart.

A.7.1. Key facts and figures

Cystic fibrosis is a multi-system genetic disorder affecting the lungs, pancreas, liver and intestine. It can have a significant impact on life expectancy and quality of life.

Cystic fibrosis is associated with a reduced life expectancy. The current median age at death is 29 years and the median predicted survival is 36.6 years.

Diagnosis is primarily made during newborn screening. The median age at diagnosis is 3 months, and 1 in every 2500 babies born in the UK has cystic fibrosis. More than 57% of people on the UK cystic fibrosis registry are aged over 16 years.

Many different mutations are responsible for cystic fibrosis. The UK registry shows 90.8% of people with cystic fibrosis have one genotype; however 8.9% of people have at least one unknown genotype.

Lung function is often reduced in cystic fibrosis. The typical measure of lung function is forced expiratory volume in 1 second (FEV1). A FEV1 of 50% and above will enable people to live relatively normal lives, and is associated with fewer difficulties in completing activities of daily living. A FEV1 above 85% indicates normal or near-normal lung function.

Lung infections are a cause of significant morbidity in cystic fibrosis. Chronic infection (for example with Staphyloccus aureus and Pseudomonas aeruginosa) may need long-term use of antibiotics.

A.7.2. Current practice

Best practice for cystic fibrosis suggests that people with the condition benefit from a multidisciplinary team approach. Such teams include physicians or paediatricians with sufficient time in their job plans allocated to the disease, supported by specialist nurses, dietitians, physiotherapists, pharmacists, social workers, clinical microbiologists and clinical psychologists.

To provide sufficient multidisciplinary team experience for the management of this complex disease, people with cystic fibrosis are grouped together into specialist centres for treatment. In these centres, outpatient care is the basis of management. Patients should be monitored at least 4 times a year by the multidisciplinary team, including annual screening to assess their progress (Service specifications 2013/14, Clinical Reference Group cystic fibrosis NHS England).

Children with cystic fibrosis may be seen in conjunction with local paediatricians and their multidisciplinary teams (a shared-care model) for the convenience of their carers. Such shared-care arrangements are not supported in the adult sector, where everyone attends specialist centres except when population density and geography make travel a problem.

For inpatient care, it is considered that all people with cystic fibrosis should be admitted to single rooms with en-suite facilities on wards run by experienced cystic fibrosis staff (Service specifications 2013/14, Clinical Reference Group cystic fibrosis NHS England). Cross-infection between people with cystic fibrosis is a serious risk, and all centres and clinics should have robust protocols in place aimed at preventing it.

There is variation both in the multidisciplinary team structures and arrangements for providing care, and in the resources available to support services. Particular problems may arise with smaller shared care clinic arrangements. In some centres, both inpatient and outpatient facilities are limited. For example, there may be problems in arranging admission to single rooms with en-suite facilities. If adequate protocols are not in place, then there is a risk of cross-infection.

By producing a robust evidence-based approach to defining best practice in cystic fibrosis care, this guideline will help improve healthcare for this highly complex condition.