Cystic Fibrosis: Diagnosis and Management

This Guidelines summary of the NICE cystic fibrosis guideline covers the key points for primary care, including diagnosis, support, and long-term management.

Diagnosis of Cystic Fibrosis

• Be aware that cystic fibrosis can be diagnosed based on:
  • positive test results in people with no symptoms, for example infant screening (blood spot immunoreactive trypsin test) followed by sweat and gene tests for confirmation or
  • clinical manifestations, supported by sweat or gene test results for confirmation or
  • clinical manifestations alone, in the rare case of people with symptoms who have normal sweat or gene test results
• Assess for cystic fibrosis and, when clinically appropriate, perform a sweat test (for children and young people) or a cystic fibrosis gene test (for adults) in people with any of the following:
  • family history
  • congenital intestinal atresia
  • meconium ileus
  • symptoms and signs that suggest distal intestinal obstruction syndrome faltering growth (in infants and young children)
  • undernutrition
  • recurrent and chronic pulmonary disease, such as:
    • recurrent lower respiratory tract infections
    • clinical or radiological evidence of lung disease (in particular bronchiectasis)
    • persistent chest X-ray 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
• 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 1 or more cystic fibrosis mutations.

Information and Support

• Provide people who are newly diagnosed with cystic fibrosis and their family members or carers (as appropriate) with opportunities to discuss their concerns
• Information and support should be provided by healthcare professionals with expertise in cystic fibrosis
• Provide people with suspected or diagnosed cystic fibrosis and their family members or carers (as appropriate) with relevant information that they can understand, and opportunities for discussion on topics such as:
  • their diagnosis
  • monitoring of their condition
  • management choices for their condition
  • possible or existing complications or comorbidities
  • implications for living independently
• Provide people with cystic fibrosis and their family members or carers (as appropriate) with information about their care pathway
• Give information to people with cystic fibrosis and to family members or carers in ways that are individually appropriate. Avoid jargon and use formats that they prefer, for example:
  • face-to-face discussions
  • copies of correspondence
  • written information (such as leaflets)
  • any digital media and reliable internet sources that are available
• When appropriate, provide people with cystic fibrosis and their family members or carers with opportunities for discussion with relevant expert professionals on:
  • available resources and support, such as local support and advocacy services 
  • managing the risks of cross-infection
  • implications of the condition for school and education
  • career planning
  • transition to adult care
  • foreign travel
  • fertility and contraception
  • pregnancy and parenting
  • organ transplantation
  • end of life care
• Provide people with cystic fibrosis with information about how to contact other people with cystic fibrosis without risking cross‑infection (see the section Preventing cross‑infection), for example by directing them to online support groups
• For more information on communication, providing information and shared decision‑making in adult NHS services, see the NICE guideline on patient experience in adult NHS services
• Be aware that people with cystic fibrosis and their family members or carers will need emotional support and some may need specialist psychological support (see the full guideline for recommendations on psychological assessment), in particular:
  • at diagnosis
  • at times of transition (for example, when starting or changing school, moving from education to work, or changing to living independently for the first time)
  • in relation to fertility, including family planning, pregnancy and infertility
  • to cope with complications of cystic fibrosis
  • when waiting for or having organ transplantation
  • when approaching the end of life.

Service Delivery

Service Configuration

• Care for people with cystic fibrosis should be provided by a specialist cystic fibrosis multidisciplinary team based at a specialist cystic fibrosis centre (see the section Multidisciplinary team)
• When a shared-care model is used for children and young people, it should include:
  • formal arrangements between the local paediatric team at the shared-care centre and the multidisciplinary team at the specialist cystic fibrosis centre
  • direct involvement of specialist cystic fibrosis multidisciplinary team members
  • an annual assessment and at least one other review per year by the specialist cystic fibrosis multidisciplinary team, in addition to reviews by the local paediatric team (see the section Annual and routine reviews)
• If available and when clinically appropriate, outreach care for adults with cystic fibrosis may be provided by the specialist cystic fibrosis multidisciplinary team at a local hospital
• Consider telemedicine or home visits for routine monitoring when they are more appropriate than outpatient visits and if the person with cystic fibrosis prefers it
• Make arrangements (including providing equipment and expert support) for people to have intravenous antibiotic therapy at home, when this is appropriate.

Multidisciplinary Team

• The specialist cystic fibrosis multidisciplinary team should include at least one of each (depending on the size of the clinic) of the following professionals, who should have specialist expertise in the condition:
  • specialist paediatricians or adult physicians 
  • specialist nurses
  • specialist physiotherapists
  • specialist dietitians
  • specialist pharmacists
  • specialist clinical psychologists
• The specialist cystic fibrosis multidisciplinary team should work with GPs, and provide timely information so that GPs can support people with cystic fibrosis by:
  • prescribing cystic fibrosis medicines:
    • in batches of at least 1 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.

Transition to Adult Services

• Begin discussing the transition process to adult services with young people with cystic fibrosis when they are 12 years old, and with their family members or carers (as appropriate)
• All cystic fibrosis services should have a coordinated and documented pathway for transition from children’s to adults’ services that includes plans for managing all cystic‑fibrosis‑related aspects of care
• Ask people with cystic fibrosis and their family members or carers (as appropriate) for feedback on the quality of the transition service, taking account of the section on planning and developing transition services in the NICE guideline on transition for young people using health or social care services
• For more guidance on managing transition from children’s to adults’ services, see the NICE guideline on transition for young people using health or social care services. In particular, see the sections on:
  • transition planning, for guidance on when transition should happen
  • named workers
  • overarching principles, for guidance on joint responsibility and working together with other organisations.

Complications of Cystic Fibrosis

• Be aware that people with cystic fibrosis are at risk of the following common complications:
  • being underweight
  • meconium ileus (affects 1 in 7 newborn babies)
  • fat-soluble vitamin deficiencies (including vitamins A, D, E and K)
  • distal intestinal obstruction syndrome
  • 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 (the 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 1 in 2 adults)
  • reduced bone mineral density (including osteoporosis)
• Be aware that people with cystic fibrosis are at risk of the following less common complications:
  • cystic‑fibrosis‑related arthritis
  • delayed puberty (associated with severe cystic fibrosis)
  • renal calculi (incidence increases with age and 1 in 20 adults are affected).

Annual and Routine Reviews

• Be aware that:
  • the aim of cystic fibrosis care is to prevent or limit symptoms and complications of the condition
  • routine monitoring and annual assessments are crucial in providing effective care
• Offer people with cystic fibrosis a comprehensive annual review that includes the following:
  • a pulmonary assessment (see Pulmonary monitoring)
  • an assessment of nutrition and intestinal absorption (see full guideline for recommendations on nutritional interventions and exocrine pancreatic insufficiency)
  • an assessment for liver disease (see Liver disease)
  • testing for cystic-fibrosis-related diabetes, from 10 years of age (see Cystic‑fibrosis‑related diabetes)
  • an assessment for other potential or existing cystic fibrosis complications (see the section Complications of cystic fibrosis)
  • a psychological assessment (see full guideline for recommendations on psychological assessment)
  • assessments by a specialist nurse, physiotherapist, pharmacist and social worker (see Service delivery)
  • a review of their exercise programme (see the section Exercise)
• Provide regular routine reviews for people with cystic fibrosis, and do these more frequently immediately after diagnosis and in early life. For example:
  • weekly in their first month of life
  • every 4 weeks when they are between 1 and 12 months old
  • every 6 to 8 weeks when they are between 1 and 5 years old
  • every 8 to 12 weeks when they are over 5 years old
  • every 3 to 6 months as adults.

Pulmonary Monitoring, Assessment and Management

Pulmonary Monitoring

• For people with cystic fibrosis who have clinical evidence of lung disease, base the frequency of routine reviews on their clinical condition but review children and young people at least every 8 weeks and adults at least every 3 months. If appropriate, think about using the review schedules above
• Include the following at each routine review, in relation to pulmonary assessment, for people with cystic fibrosis:
  • a clinical assessment, including a review of clinical history and medicines adherence, and a physical examination with measurement of weight and length or height
  • measurement of oxygen saturation
  • taking respiratory secretion samples for microbiological investigations, using sputum samples if possible, or a cough swab or nasal pharyngeal aspirate (NPA)
  • lung function testing with spirometry (including forced expiratory volume in 1 second [FEV₁], forced vital capacity [FVC], and forced expiratory flow [FEF] 25–75%) in adults, and in children and young people who can do this
• If spirometry is normal at a routine review, consider measuring lung clearance index
• Include the following at each annual review in relation to pulmonary assessment for people with cystic fibrosis:
  • a clinical assessment, including a review of the clinical history and medicines adherence, and a physical examination, with measurement of weight and length or height
  • a physiotherapy assessment
  • measurement of oxygen saturation
  • a chest X-ray
  • blood tests, including white cell count, aspergillus serology and serum IgE
  • taking respiratory secretion samples for microbiological investigations (including non-tuberculous mycobacteria)
  • lung function testing (for example with spirometry, including FEV₁, FVC, and FEF 25–75%) in adults, and in children and young people who can do this
• Consider measuring lung clearance index at each annual review if spirometry is normal
• For people with cystic fibrosis with lung disease who have symptoms that are concerning them or their family members or carers (as appropriate), consider which of the following may be useful:
  • review of clinical history
  • physical examination, including measurement of weight and length or height
  • measurement of oxygen saturation
  • taking respiratory secretion samples for microbiological investigations, using sputum samples if possible, or a cough swab or NPA if not
  • for adults, blood tests to measure white cell count and inflammatory markers such as C-reactive protein
  • lung function testing, for example with spirometry (including FEV₁, FVC, and FEF 25–75%) in adults, and in children and young people who can do this
  • lung clearance index for people with normal spirometry resultsDepending on the assessments that are needed, decide whether to provide a remote telemedicine or face-to-face assessment
• Think about doing a low-dose chest CT scan for children with cystic fibrosis who have not had a chest CT scan before, to detect features that other tests (such as a plain chest X-ray) would miss (for example early bronchiectasis)
• Think about doing a chest X-ray for people with cystic fibrosis during or after treatment for an exacerbation of lung disease (taking account of severity), if:
  • the exacerbation does not respond to treatment or
  • a chest X-ray before treatment showed new radiological abnormalities
• Monitor the treatment response during and after an exacerbation of lung disease by assessing whether the symptoms and signs have resolved, and as appropriate:
  • take respiratory secretion samples for microbiological investigations, using sputum samples if possible, or a cough swab or NPA if not
  • test lung function, for example with spirometry (including FEV₁, FVC and FEF 25–75%) in adults, and in children and young people who can do this
  • measure oxygen saturation
• Think about using broncho-alveolar lavage to obtain airway samples for microbiological investigation in people with cystic fibrosis if:
  • they have lung disease that has not responded adequately to treatment and
  • the cause of the disease cannot be found with non-invasive upper airway respiratory secretion sampling (including sputum induction if appropriate).

Airway Clearance Techniques

• Discuss the use of airway clearance techniques with people with cystic fibrosis who do not have clinical evidence of lung disease and their parents or carers (as appropriate). Provide them with training in airway clearance techniques and explain when to use them
• Offer training in airway clearance techniques to people with cystic fibrosis who have clinical evidence of lung disease and their parents or carers (as appropriate)
• When choosing an airway clearance technique for people with cystic fibrosis:
  • assess their ability to clear mucus from their lungs, and offer an individualised plan to optimise this
  • take account of their preferences and (if appropriate) those of their parents and carers
  • take account of any factors that may influence adherence
• Regularly assess the effectiveness of airway clearance techniques, and modify the technique or use a different one if needed
• Do not offer high-frequency chest wall oscillation as an airway clearance technique for people with cystic fibrosis except in exceptional clinical circumstances. The specialist cystic fibrosis team will decide whether these circumstances apply, and their decision would then be subject to the NHS England policy on Individual Funding Requests. Be aware that the evidence shows high-frequency chest wall oscillation is not as effective as other airway clearance techniques
• Consider using non-invasive ventilation in people with cystic fibrosis who have moderate or severe lung disease and cannot clear their lungs using standard airway clearance techniques.

Mucoactive Agents

• Offer a mucoactive agent to people with cystic fibrosis who have clinical evidence of lung disease
• Offer rhDNase (dornase alfa; recombinant human deoxyribonuclease)^[A] as the first choice of mucoactive agent
• If clinical evaluation or lung function testing indicates an inadequate response to rhDNase, consider both rhDNase^[A] and hypertonic sodium chloride or hypertonic sodium chloride alone
• Consider mannitol dry powder for inhalation^[B] for children and young people who cannot use rhDNase and hypertonic sodium chloride because of ineligibility, intolerance or inadequate response
• Mannitol dry powder for inhalation is recommended as an option for treating cystic fibrosis in adults:
  • who cannot use rhDNase because of ineligibility, intolerance or inadequate response to rhDNase and
  • whose lung function is rapidly declining (forced expiratory volume in 1 second [FEV₁] decline greater than 2% annually) and
  • for whom other osmotic agents are not considered appropriate [This recommendation is from mannitol dry powder for inhalation for treating cystic fibrosis (NICE technology appraisal guidance 266)]
• People currently receiving mannitol whose cystic fibrosis does not meet the above criteria should be able to continue treatment until they and their clinician consider it appropriate to stop. [This recommendation is from mannitol dry powder for inhalation for treating cystic fibrosis (NICE technology appraisal guidance 266)]
• For recommendations on using lumacaftor–ivacaftor, see the NICE technology appraisal guidance on lumacaftor–ivacaftor for treating cystic fibrosis homozygous for the F508del mutation.

Pulmonary Infection

Unidentified Infections

• For people with cystic fibrosis who have a pulmonary disease exacerbation and no clear cause (based on recent respiratory secretion sample cultures):
  • use an oral or intravenous (depending on the exacerbation severity) broad-spectrum antibiotic
  • continue collecting respiratory secretion samples, and change treatments if a pathogen is identified and a more appropriate treatment is available.

Immunomodulatory Agents

• For people with cystic fibrosis and deteriorating lung function or repeated pulmonary exacerbations, offer long‑term treatment with azithromycin^[C] at an immunomodulatory dose
• For people who have continued deterioration in lung function, or continuing pulmonary exacerbations while receiving long-term treatment with azithromycin, stop azithromycin and consider oral corticosteroids
• Do not offer inhaled corticosteroids as an immunomodulatory treatment for cystic fibrosis.

Other Monitoring, Assessment and Management

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
• Suspect distal intestinal obstruction syndrome in people with cystic fibrosis who have an acute onset of peri-umbilical or right lower quadrant abdominal pain and any of the following:
  • a palpable mass in the right lower quadrant
  • faecal loading in the right lower quadrant on a plain abdominal X-ray, especially if associated with small intestine air-fluid levels
  • clinical features of partial or complete intestinal obstruction, such as vomiting (especially bilious) and abdominal distension
• For people who have an acute onset of peri-umbilical abdominal pain but no other clinical or radiological features of distal intestinal obstruction syndrome, consider further imaging, for example with an:
  • abdominal ultrasound scan or
  • abdominal CT scan
• 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.

Liver Disease

• Perform a clinical assessment and liver function blood tests at the annual review for people with cystic fibrosis
• If liver function blood tests are abnormal, perform a liver ultrasound scan and consider ursodeoxycholic acid treatment^[D]
• Think about stopping ursodeoxycholic acid if liver function blood tests return to normal and clinical assessment and liver ultrasound scan show no liver disease
• If ursodeoxycholic acid is stopped, monitor for re-emergence of liver disease using clinical assessment and liver function blood tests
• Think about referring people with cystic fibrosis to a liver specialist if the liver function blood test results are persistently abnormal despite treatment with ursodeoxycholic acid
• Refer people with cystic fibrosis to a liver specialist if they have any of the following:
  • chronic progressive liver disease, based on clinical assessment, liver function blood tests or the findings on a liver ultrasound scan
  • liver failure, based on clinical assessment and liver function tests
  • portal hypertension, haematemesis, splenomegaly or findings on a liver ultrasound scan.

Cystic-fibrosis-related Diabetes

• Diagnose cystic‑fibrosis‑related diabetes using one of the following:
  • continuous glucose monitoring (CGM)
  • serial glucose testing over several days
  • oral glucose tolerance testing (OGTT) – if OGTT is abnormal perform CGM or serial glucose testing over several days to confirm the diagnosis
• Test for cystic-fibrosis-related diabetes (as above) in people with cystic fibrosis annually from 10 years of age
• Test for cystic-fibrosis-related diabetes at the end of the first and second trimesters of pregnancy, using CGM or OGTT
• Test for cystic-fibrosis-related diabetes in people with cystic fibrosis who are taking long-term systemic corticosteroids or receiving enteral tube feeding, using CGM or serial glucose monitoring
• Think about testing for cystic‑fibrosis‑related diabetes in people who still have any of the following despite optimised cystic fibrosis treatment:
  • unexplained weight loss
  • a deterioration in lung function as measured by spirometry
  • increased frequency of pulmonary exacerbations
  • excessive tiredness.

Bone Mineral Density

• Consider dual energy X‑ray absorptiometry (DXA) 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 oral corticosteroid use 
  • frequent intravenous antibiotic use
  • severe lung disease
  • undernutrition
  • previous low-impact fractures
  • previous transplants
  • post menopause
• Seek specialist advice for people with a bone mineral density standard deviation below -2.0 (Z score) or -2.5 (T score).

Exercise

• Advise people with cystic fibrosis and their family members or carers (as appropriate) that regular exercise improves both lung function and overall fitness
• Offer people with cystic fibrosis an individualised exercise programme, taking into account their capability and preferences
• Regularly review exercise programmes to monitor the person’s progress and ensure that the programme continues to be appropriate for their needs
• Provide people with cystic fibrosis who are having inpatient care with:
  • an assessment of their exercise capacity
  • the facilities and support to continue their exercise programme (as appropriate), taking into account the need to prevent cross‑infection (see preventing cross‑infection, below) and local infection control guidelines.

Preventing Cross-infection

• For recommendations on preventing and controlling infection, see the NICE guidelines on infection control in primary and community care and healthcare‑associated infections, and the NICE quality standard on infection prevention and control
• To prevent cross-infection among people with cystic fibrosis in outpatient and inpatient care, use microbiological surveillance and a local infection control strategy that includes cohorting
• 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.

For recommendations on service configuration, the multidisciplinary team, pulmonary infections, nutritional interventions and exocrine pancreatic insufficiency, distal intestinal obstruction syndrome, psychological assessment, and preventing cross-infection, refer to the full guideline. 

Footnotes

[A] At the time of publication (October 2017), rhDNase did not have a UK marketing authorisation for use in children under 5 years of age with cystic fibrosis for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information.

[B] At the time of publication (October 2017), mannitol dry powder for inhalation did not have a UK marketing authorisation for use in children with cystic fibrosis for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information.

[C] At the time of publication (October 2017), azithromycin did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information.

[D] At the time of publication (October 2017), ursodeoxycholic acid did not have a UK marketing authorisation for adults with cystic fibrosis for this indication. The prescriber should check individual brands for licensing in children and young people and follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Prescribing guidance: prescribing unlicensed medicines for further information.