Intended for healthcare professionals

Practice Guidelines

Diagnosis and management of cystic fibrosis: summary of NICE guidance

BMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j4574 (Published 26 October 2017) Cite this as: BMJ 2017;359:j4574
cropped thumbnail of infographic

Infographic available

A visual summary of monitoring and assessment approaches for people with cystic fibrosis

  1. Gemma Villanueva, senior systematic reviewer1,
  2. Gemma Marceniuk, health economist1,
  3. M Stephen Murphy, clinical adviser1,
  4. Martin Walshaw, chair of guideline committee and honorary professor of medicine2,
  5. Rami Cosulich, systematic reviewer1
  6. on behalf of the Guideline Committee
  1. 1National Guideline Alliance, Royal College of Obstetricians and Gynaecologists, London
  2. 2Regional Cystic Fibrosis Clinic, Liverpool Heart and Chest Hospital, University of Liverpool, UK
  1. Correspondence to: Rami Cosulich RCosulich{at}rcog.org.uk

What you need to know

  • Some people with cystic fibrosis (including adults) are undiagnosed because they missed the newborn screening process; they carry less common cystic fibrosis mutations; or have atypical manifestations of cystic fibrosis

  • Common complications associated with cystic fibrosis that might be identified in primary care include malnutrition, liver disease, infertility, and reduced bone mineral density

  • Forced expiratory volume in 1 second (FEV1) is the typical measure of lung function and a key predictor of life expectancy in people with cystic fibrosis

  • Optimising lung function is a major goal in cystic fibrosis care

  • Exercise is advised in cystic fibrosis to help maintain and slow the decline in respiratory function, facilitate airway clearance techniques, help improve bone mineral density, and to increase and maintain muscle strength, flexibility, and posture

Cystic fibrosis is a life limiting autosomal recessive disorder that affects up to one in 2500 babies born in the UK. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator protein, which acts at the cell surface in all mucus producing organs in the body. It is a multisystem disorder, affecting the lungs, pancreas, liver, and intestine. It is usually diagnosed in the UK through a neonatal screening programme, although diagnosis can be made later, and even in adult life.1 The median age at diagnosis is 2 months.1 In the past, when early death was common, cystic fibrosis was uncommon in adults, but with improved management this is no longer the case in more developed countries. However, in low income countries, mortality in childhood is still high.2 At present, more than 60% of people on the UK cystic fibrosis registry are aged over 16.1

This article summarises the recent National Institute for Health and Care Excellence (NICE) guidance on the diagnosis and management of cystic fibrosis in children, young people, and adults.3

This guideline was commissioned with the aim of improving the diagnosis and management of cystic fibrosis. It covers indications for referral, diagnosis, monitoring, and recognition of complications. It addresses the management of pulmonary disease, including infection in cystic fibrosis, and the prevention of cross infection. It also provides recommendations on service organisation, information, and support to people with cystic fibrosis, and where appropriate to parents and carers.

Although the guideline recommends that the care of people with cystic fibrosis is provided by specialist cystic fibrosis centres, this summary is specifically aimed at non-specialist healthcare professionals, for example in primary care, who might become involved in the care of people with cystic fibrosis for a variety of reasons. Healthcare professionals might need to recognise complications of the condition (for example, fertility problems), or when to signpost on to other services.

Recommendations

NICE recommendations are based on systematic reviews of the best available evidence, although this is often of low or at best moderate quality, and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Committee’s (GC) experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets.

When should cystic fibrosis be suspected?

Most people with cystic fibrosis are diagnosed during newborn screening. According to the UK Cystic Fibrosis Registry, 180 babies born in 2016 were identified by newborn screening, and the median age at diagnosis was 2 months.1 However, the screening programme was introduced UK-wide in mid-2007, therefore there remains a cohort of young people and adults who have not been screened.1 Furthermore, those with rarer mutations or atypical manifestations of cystic fibrosis (for example, those with mild respiratory symptoms or males with infertility) can reach adulthood undiagnosed.4 Nine hundred and thirty five adults (16.1%) with cystic fibrosis in the UK Cystic Fibrosis Registry in 2016 had been diagnosed at age 16 or after.1 This recommendation aims to help healthcare professionals, including primary care clinicians, to identify what symptoms might indicate a possibility of cystic fibrosis and so warrant further investigation.

  • Assess for cystic fibrosis (fig 1) (taking into account clinical history and examination, and presence of these indicators) and, when clinically appropriate, perform a sweat test (for children and young people) or a cystic fibrosis gene test (for adults) (box 1) in people with any of the following:

    • family history

    • congenital intestinal atresia

    • meconium ileus

    • symptoms and signs that suggest distal intestinal obstruction syndrome (for example, acute pain and evidence of stool retention in the distal ileum)

    • faltering growth (in infants and young children4)

    • undernutrition (in older children and adults)

    • recurrent and chronic pulmonary disease, such as:

      • recurrent lower respiratory tract infections

      • clinical or radiological evidence of lung disease (in particular bronchiectasis)

      • persistent chest radiograph changes

      • chronic wet or productive cough

    • chronic sinus disease

    • obstructive azoospermia (in young people and adults)

    • acute or chronic pancreatitis

    • malabsorption

    • rectal prolapse (in children)

    • pseudo-Bartter syndrome.

      [Based on the experience and opinion of the GC and very low quality evidence from observational studies]

  • Refer people with suspected cystic fibrosis to a specialist cystic fibrosis centre if:

    • they have a positive or equivocal sweat test result

    • their assessment suggests they have cystic fibrosis but their test results are normal

    • gene testing reveals one or more cystic fibrosis mutations.

      [Based on the experience and opinion of the GC]

Box 1: Testing for cystic fibrosis

Sweat test

This measures the concentration of chloride in sweat. The sweat in a person with cystic fibrosis has a high concentration of salt, and a sweat chloride >60 mmol/L is suggestive of cystic fibrosis.5 Sweat tests are performed at paediatric clinics (patients will need referral) and those results could prompt a referral to specialist cystic fibrosis centres for further investigation and the initiation of cystic fibrosis related treatment.

Gene test

The gene test for cystic fibrosis is a simple blood test that can be taken by any healthcare professional and sent to the district general hospital laboratory, which will then send it on to a genetic laboratory for testing. The result comes back within one month. Any form of positive/part positive result should be referred to the specialist cystic fibrosis centre, as per the guideline.

Figure1

Fig 1 Assessment for cystic fibrosis. Based on this BMJ summary of NICE guidance and the authors’ experience

What are the most common complications of cystic fibrosis?

People with cystic fibrosis might present to primary or secondary care with any of several common complications (box 2, infographic).

Box 2: Complications of cystic fibrosis

Common complications
  • Being underweight (for example, having a low body mass index)

  • Meconium ileus (affects one in seven newborn babies)

  • Fat soluble vitamin deficiencies (including vitamins A, D, E, and K)

  • Distal intestinal obstruction syndrome (this might present with acute pain and evidence of stool retention in the distal ileum)

  • Muscle pains and arthralgia

  • Male infertility caused by obstructive azoospermia (almost all males with cystic fibrosis are infertile)

  • Reduced female fertility

  • Upper airway complications, including nasal polyps and sinusitis (prevalence increases with age)

  • Chronic liver disease (prevalence increases with age until early adulthood)

  • Urinary stress incontinence

  • Cystic fibrosis related diabetes (uncommon in children under 10 years, but the prevalence increases with age and it affects up to half of adults)

  • reduced bone mineral density (including osteoporosis).

[Based on the experience and opinion of the GC and very low to high quality evidence from observational studies and from the UK CF Registry]

Less common complications
  • Cystic fibrosis related arthritis

  • Delayed puberty (associated with severe cystic fibrosis)

  • Renal calculi (incidence increases with age and one in 20 adults are affected).

[Based on the experience and opinion of the GC and very low to high quality evidence from observational studies and from the UK CF Registry]

Recommendations for assessment and management of complications

  • Management of distal intestinal obstruction syndrome:

    • Be aware that a variety of conditions can cause acute abdominal pain and resemble distal intestinal obstruction syndrome in people with cystic fibrosis, for example, constipation, appendicitis, intussusception, cholecystitis.

    • Manage suspected distal intestinal obstruction syndrome in a specialist cystic fibrosis centre, with supervision from specialists who have expertise in recognising and treating the condition and its complications.

    • [Based on the experience and opinion of the GC]

  • Surveillance for reduced bone mineral density:

    • The cystic fibrosis centre should consider dual energy x ray absorptiometry bone density scans for people with cystic fibrosis who have factors that put them at high risk of low bone mineral density, such as frequent or long term use of oral corticosteroids, frequent use of intravenous antibiotics, severe lung disease, undernutrition, previous low impact fractures, previous transplants, post menopause.

    • [Based on the experience and opinion of the GC and very low to moderate quality evidence from longitudinal studies]

  • Surveillance for cystic fibrosis related diabetes:

    • Cystic-fibrosis-related diabetes should be tested at the cystic fibrosis centre in people with cystic fibrosis annually from 10 years of age.

    • Additional tests should be performed during pregnancy and in people who are taking long term systemic corticosteroids or receiving enteral tube feeding.

      [Based on the experience and opinion of the GC]

  • Surveillance for cystic fibrosis related liver disease and prevention of progression:

    • The cystic fibrosis centre should perform a clinical assessment and liver function blood tests at the annual review for people with cystic fibrosis

    • [Based on the experience and opinion of the GC and on very low to high quality evidence from cohort and case control studies]

    • People with liver disease may require ursodeoxycholic acid treatment and sometimes referral to a liver specialist if liver tests remain abnormal after treatment.

    • [Based on the experience and opinion of the GC and on low to high quality evidence from randomised controlled trials]

  • Detection, monitoring, and management of nutritional problems and exocrine pancreatic insufficiency:

    • Encourage people to increase calorie intake by increasing portion size and eating high energy foods if there is concern about their nutrition (including weight loss and inadequate weight gain)

    • [Based on the experience and opinion of the GC]

    • The specialist dietitian at the cystic fibrosis centre should consider a trial of oral nutritional supplements if increased portion size and high energy foods are not effective

    • [Based on very low to high quality evidence from randomised controlled trials and on the experience and opinion of the GC]

    • The cystic fibrosis centre should test for exocrine pancreatic insufficiency in people with cystic fibrosis, using a non-invasive technique.

    • [Based on the experience and opinion of the GC]

  • Psychological support:

    • Recognising the emotional impact of cystic fibrosis, the guideline committee made a recommendation to offer people with cystic fibrosis an annual review with a specialist clinical psychologist through their specialist centre. The annual review should be individualised, depending on the circumstances of the person and might cover aspects such as general mental health and quality of life, behavioural problems affecting health outcomes, adherence to treatment, school attendance, friendship, and social life.

    • [Based on the experience and opinion of the GC]

Longer term care for people with cystic fibrosis (infographic)

Routine reviews

  • Regular routine reviews conducted by the specialist cystic fibrosis team are critical to prevent or limit symptoms and complications of the condition and to provide effective care. These should be done more frequently immediately after diagnosis and in early life and less frequently (for example, every three to six months) as adults.

  • [Based on the experience and opinion of the GC]

  • The specialist clinic multidisciplinary team should offer a comprehensive annual review to include pulmonary assessment, testing for complications including diabetes and liver disease, a psychological assessment, and review of their exercise programme.

  • [Based on the experience and opinion of the GC]

What does pulmonary monitoring involve?

Each person with cystic fibrosis will have their own forced expiratory volume in 1 second (FEV1) target, based on their own lung function results and trends.

It is important to monitor the rate of decline in FEV1 to inform any subsequent changes in management to prevent FEV1 from falling as much as possible. Moreover, cystic fibrosis requires constant vigilance to enable early intervention to treat infection, and to assess the response to treatment of acute infections and exacerbations (the sudden or recent worsening of clinical symptoms or signs, frequently caused by an acute pulmonary infection).

People with cystic fibrosis might present first to their general practitioner with symptoms of a mild chest exacerbation, where it might be appropriate for the GP to offer oral antibiotics, based on their knowledge of the individual’s sputum microbiology and the guideline. Management of more serious or persistent chest exacerbations, however, would usually be done by or based on advice of specialist team.

The guideline provides detailed recommendations on monitoring strategies, it also gives recommendations on the use of antibiotics in the prevention and treatment of pulmonary infection. It specifically addresses the management of infection with Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex, Haemophilus influenzae, non-tuberculous mycobacteria, Aspergillus fumigatus complex, and non-identified infections.

Some people with cystic fibrosis might receive treatment with immunomodulatory agents to reduce pulmonary inflammation. The guideline provides recommendations on the use of the mucolytic agents (dornase alfa, hypertonic sodium chloride, and mannitol), and on the use of airway clearance techniques in those with and without clinical evidence of lung disease, and on the need for training with these techniques if they are used.

Prescribing strategies are usually initiated by the specialist pharmacist at the cystic fibrosis clinic:

  • Specialist pharmacists should advise people with cystic fibrosis on medicines optimisation at outpatient clinic visits, during inpatient admissions, on discharge from hospital, and at annual review. They should advise healthcare professionals on all aspects of medicines use and prescribing, and support GPs, community pharmacists, and homecare providers to ensure that people with cystic fibrosis get the medicines they need without interruption.

  • [Based on the experience and opinion of the GC]

What are the benefits of exercise in cystic fibrosis?

Exercise should be a routine part of the management of cystic fibrosis. In addition to the benefits found in the general population, exercise participation is advised in cystic fibrosis to help maintain and slow the decline in respiratory function, facilitate airway clearance techniques, help improve bone mineral density, and increase and maintain muscle strength, flexibility, and posture.

  • Advise people with cystic fibrosis and their family members or carers (as appropriate) that regular exercise improves both lung function and overall fitness.

  • [Based on the experience and opinion of the GC and very low to moderate quality evidence from randomised controlled trials and cohort studies]

Awareness of cross infection

It is important for all healthcare professionals, including in primary care, to be aware of the concerns regarding cross infection between people with cystic fibrosis, for example with specific pathogens such as P. aeruginosa.

  • Inform people with cystic fibrosis, their family members or carers (as appropriate) and staff involved in their care about the risk of cross infection and how to avoid it. [Based on the experience and opinion of the GC]

Service delivery

How services are organised

In the UK, care for children with cystic fibrosis is provided by a specialist cystic fibrosis centre.

The specialist care of people with cystic fibrosis requires an expert team of cystic fibrosis specialist healthcare professionals. The multidisciplinary team works in partnership with primary care services (box 3) and includes or has access to a wide range of specialists such as palliative and social care.

Box 3: What is the role of primary care?

  • The specialist cystic fibrosis multidisciplinary team should work with GPs, and provide timely information so that GPs can support the person with cystic fibrosis by:

    • prescribing routine cystic fibrosis medicines

      • in batches of at least one month at a time for routine medicines

      • for longer periods if advised by the specialist team

      • following guidance on arrangements for prescriptions of unlicensed medicines

    • providing routine annual immunisation, including any alterations for people with cystic fibrosis and flu vaccinations for family members and carers

    • managing health problems not related to cystic fibrosis

    • certification of illnesses

    • working in partnership with cystic fibrosis homecare teams, particularly for end of life care

    • providing care for the person’s family members or carers

    • [Based on the experience and opinion of the GC]

What information and support can be provided to people with cystic fibrosis and their parents or carers?

Access to appropriate information and support can help to reduce anxiety and increase empowerment and confidence in people with cystic fibrosis and their carers.

  • The cystic fibrosis team usually provides information on the following topics:

    • diagnosis

    • monitoring of the condition

    • managing choices for the condition

    • possible or existing complications or comorbidities

    • implications for living independently.

    • [Based on the experience and opinion of the GC and very low to moderate quality evidence from qualitative studies]

  • Provide people with cystic fibrosis and their family members or carers (as appropriate) with information about their care pathway. [Based on the experience and opinion of the GC and very low to moderate quality evidence from qualitative studies]

Resources for patients, families, and carers

These websites offer useful and reliable information for people with cystic fibrosis and their families and carers.

Guidelines into practice

  • How do you ensure that you keep in mind symptoms and signs suggestive of cystic fibrosis during assessments for children, young people, and adults?

  • Are you aware of the most common complications in people with cystic fibrosis?

  • What might you do differently as a result of reading this article?

Further information on the guidance

Methods

This guidance was developed by the National Guideline Alliance in accordance with NICE guideline development methods (https://www.nice.org.uk/media/default/about/what-we-do/our-programmes/developing-nice-guidelines-the-manual.pdf).

A Guideline Committee was established by the National Guideline Alliance, which incorporated healthcare and allied healthcare professionals (one adult physiotherapist, one adult specialist nurse, one advanced physiotherapist, one consultant and honorary reader in respiratory medicine and cystic fibrosis, one consultant in respiratory paediatrician, one consultant physician in general and chest medicine, one cystic fibrosis specialist dietitian, one general paediatrician, one honorary professor of medicine, one paediatric nurse specialist (children and young people) cystic fibrosis, one principal paediatric dietitian, one senior consultant clinical psychologist, one senior pharmacist paediatrics and cystic fibrosis, and one senior respiratory pharmacist) and two lay members. In addition, the Committee had two co-opted members (one consultant medical microbiologist and one dean at school of medicine, dentistry, and biomedical sciences).

The Committee identified relevant clinical questions, collected and appraised clinical evidence, and evaluated the cost effectiveness of proposed interventions where possible. Qualitative reviews were undertaken to explore aspects related to information and support.

Quality ratings of the evidence were based on GRADE methodology (www.gradeworkinggroup.org/). These relate to the quality of the available evidence for assessed outcomes or themes rather than the quality of the study.

The scope and the draft of the guideline went through a rigorous reviewing process, in which stakeholder organisations were invited to comment; the group took all comments into consideration when producing the final version of the guideline.

Three different versions of this guideline have been produced: a full version containing all the evidence, the process undertaken to develop the recommendations, and all the recommendations, known as the “Full guideline”; a short version containing a list of all the recommendations, known as the “Short guideline”; and a version on the information for patients product, known as the “Information for the public guideline.” All of these versions are available from the NICE website (http://www.nice.org.uk/ng78).

A formal review of the need to update a guideline is usually undertaken by NICE after its publication. NICE will conduct a review to determine whether the evidence base has progressed significantly to alter the guideline recommendations and warrants an update.

Future research

The Guideline Committee prioritised the following research recommendations:

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

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

  3. 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?

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

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

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

How patients were involved in the creation of this article

Patients were not directly involved in this article. Committee members involved in this guideline included two patient representatives (one mother of twins with cystic fibrosis and one young adult with cystic fibrosis), who contributed to the formulation of the recommendations summarised here.

Footnotes

  • The members of the guideline committee were Mandy Bryon, Janis Bloomer, Sarah Collins, Alexander Darlington, Iolo Doull, Elaine Edwards, Zoe Elliott, Andrew Jones, David Lacy, Nichola MacDuff, Helen McCabe, Helen Parrott, Sarah Popple, Keith Thompson and Martin Walshaw. The co-opted members were Stuart Elborn and Stephen Holden.

    The members of the National Guideline Alliance technical team were Omnia Abdulrazeg (until January 2016), Stephanie Arnold (from May 2016), Alexander Bates (November 2016–January 2017), Zosia Beckles (until March 2016), Bishal Bhandari (September 2016–November 2016), Lisa Boardman (from January 2017), Me’leshah Brown, Shona Burman-Roy Reviewer (March 2015–May 2016), Rami Cosulich (from March 2016), Katherine Cullen (until December 2014), Vanessa Delgado-Nunes (until November 2016), Annabel Flint (until September 2016), Paul Jacklin (January 2015–July 2015), Gemma Marceniuk (from July 2015), Maija Kallioinen (August 2016–September 2016), Stephen Murphy, Fionnuala O’Brien (from September 2016), Hugo Pedder, Gemma Villanueva (from March 2015).

  • Contributors: All authors contributed to the initial draft of this article, helped revise the manuscript, and approved the final version for publication.

  • Funding: The National Guideline Alliance was commissioned and funded by the National Institute for Health and Care Excellence to develop this guideline and write this BMJ summary.

  • Competing interests: We declare the following interests based on NICE's policy on conflicts of interests (available at www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/code-of-practice-for-declaring-and-managing-conflicts-of-interest.pdf). The authors’ full statements can be viewed at www.bmj.com/content/bmj/355/bmj.i6385/related#datasupp.

  • Provenance and peer review: Commissioned; not externally peer reviewed

References

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