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European Cystic Fibrosis Society Standards of Care: Best Practice guidelinesMon, 08/18/2014 - 19:00
Specialised CF care has led to a dramatic improvement in survival in CF: in the last four decades, well above what was seen in the general population over the same period. With the implementation of newborn screening in many European countries, centres are increasingly caring for a cohort of patients who have minimal lung disease at diagnosis and therefore have the potential to enjoy an excellent quality of life and an even greater life expectancy than was seen previously. To allow high quality care to be delivered throughout Europe, a landmark document was published in 2005 that sets standards of care. Our current document builds on this work, setting standards for best practice in key aspects of CF care. The objective of our document is to give a broad overview of the standards expected for screening, diagnosis, pre-emptive treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support. For comprehensive details of clinical care of CF, references to the most up to date European Consensus Statements, Guidelines or Position Papers are provided in Table 1 . We hope that this best practice document will be useful to clinical teams both in countries where CF care is developing and those with established CF centres.
Keywords: Cystic fibrosis, Standards of care, Multidisciplinary management.
1. Newborn screening and access to specialist care from early in life
Kevin W. Southern (UK)
First author and topic Consensus (C), guideline (G) or position papers (P) Web URL Screening Castellani C  Benchmarks for cystic fibrosis carrier screening: A European consensus document (C) http://www.sciencedirect.com/science/article/pii/S1569199310000275 Castellani C  European best practice guidelines for cystic fibrosis neonatal screening (G) https://www.ecfs.eu/files/webfm/webfiles/File/documents/Castellani_2009_Journal-of-Cystic-Fibrosis.pdf Sermet-Gaudelus I  Guidelines on the early management of infants diagnosed with cystic fibrosis following newborn screening (G) http://www.sciencedirect.com/science/article/pii/S1569199310000652 Diagnosis Mayell SJ  A European consensus for the evaluation and management of infants with an equivocal diagnosis following newborn screening for cystic fibrosis (C) http://www.elsevier.com/__data/promis_misc/JCF8.pdf Castellani C  Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice (C) http://www.elsevier.com/__data/promis_misc/JCF7.pdf Bombieri C  Recommendations for the classification of diseases as CFTR-related disorders (G) https://www.ecfs.eu/files/webfm/webfiles/File/documents/JCF%20Articles/JCF10_Sup2_S86_S102.pdf Prevention of progression of lung disease Döring G  Early intervention and prevention of lung disease in cystic fibrosis: a European consensus (C) http://www.elsevier.com/__data/promis_misc/2004.pdf Optimal nutrition and management of metabolic complications Sinaasappel M  Nutrition in patients with cystic fibrosis: a European consensus (C) http://www.elsevier.com/__data/promis_misc/2002.pdf Sermet-Gaudelus I  European cystic fibrosis bone mineralisation guidelines (G) https://www.ecfs.eu/files/webfm/webfiles/File/documents/JCF%20Articles/JCF10_Sup2_S16_S23.pdf Treatment of the complications Döring G  Treatment of lung infection in patients with cystic fibrosis: current and future directions (P) https://www.ecfs.eu/ecfs-standards-care/references Colombo C  Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients (G) https://www.ecfs.eu/files/webfm/webfiles/File/documents/JCF%20Articles/JCF10_Sup2_S24_S28.pdf Debray D  Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease (G) https://www.ecfs.eu/files/webfm/webfiles/File/documents/JCF%20Articles/JCF10_Sup2_S29_S36.pdf Heijerman HJ  Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus (C) https://www.ecfs.eu/files/webfm/webfiles/File/documents/JCF_article.pdf Edenborough F  Guidelines for the management of pregnancy in women with cystic fibrosis (G) https://www.ecfs.eu/files/webfm/webfiles/File/documents/Pregnancy.pdf Tranplantation and end of life Hirche T  Practical guidelines: lung transplantation in patients with cystic fibrosis (G) http://dx.doi.org/10.1155/2014/621342 Sands D  End of life care for patients with cystic fibrosis (G) https://www.ecfs.eu/files/webfm/webfiles/File/documents/JCF%20Articles/JCF10_Sup2_S37_S44.pdf Psychosocial support Nobili R  Guiding principles on how to manage relevant psychological aspects within a CF team: interdisciplinary approaches (G) https://www.ecfs.eu/files/webfm/webfiles/File/documents/JCF%20Articles/JCF10_Sup2_S45_S52.pdf
Anne Munck (F)
Nataliya Kashirskaya (Rus)
The ECFS Neonatal Screening Working Group (Core Committee)
There is clear evidence to support newborn screening for CF. Early recognition provides the foundation for future management and prevents the delay in diagnosis that has affected so many families  . Protocols should be designed to reflect the culture and CFTR genetics of each population and minimise potential negative impacts. Please refer to the ECFS guidelines on newborn screening and on the management of young infants with CF diagnosed through screening  and .
1.1. What population characteristics validate screening newborn infants for cystic fibrosis?
Health authorities need to balance the benefit/risk ratio of screening newborns for CF in their population. If the incidence of CF is less than 1/7000 births, careful evaluation is required as to whether NBS is valid. The protocol must be shown to cause the minimum negative impact possible on the population.
1.2. What health and social resources are minimally acceptable for newborn screening to be a valid undertaking?
Infants identified with CF through a NBS programme should have prompt access to specialist CF care that achieves ECFS standards. A NBS programme may be a mechanism to better organise CF services, through the direct referral of infants for specialist CF care. Countries with limited resources should consider a pilot study to assess the validity of NBS and the adequacy of referral services for newly diagnosed infants in their population.
1.3. What is an acceptable number of repeat tests required for inadequate dried blood samples for every 1000 infants screened?
The number of requests for repeat dried blood samples should be monitored and should be less than 0.5%. More than 20 repeats for every 1000 infants are unacceptable (2%).
1.4. What is an acceptable number of false positive NBS results (infants referred for clinical assessment and sweat testing)?
Programmes should aim for a minimum positive predictive value of 0.3 (PPV is the number of infants with a true positive NBS test divided by the total number of positive NBS tests).
1.5. What is an acceptable number of false negative NBS results? These are infants with a negative NBS test that are subsequently diagnosed with CF (a delayed diagnosis)
Programmes should aim for a minimum sensitivity of 95%. Sensitivity is the number of true positive NBS results as a percentage of the total CF population (true positive and false negatives). Mechanisms should be in place for the collection of reliable long-term false negative data.
1.6. What is the maximum acceptable delay between a sweat test being undertaken and the result given to the family?
The sweat test should be analysed immediately and the result normally reported to the family on the same day.
1.7. What is the maximum acceptable age of an infant on the day they are first reviewed by a CF specialist team following a diagnosis of CF after NBS?
The majority of infants with a confirmed diagnosis after NBS should be seen by the CF specialist team by 35 days and no later than 58 days after birth. Programmes that are consistently missing these targets should undertake a protocol review and consider alternative strategies.
1.8. What is the minimum acceptable information for families of an infant recognised to be a carrier of a CF causing CFTR mutation after NBS?
- a) Families should receive a verbal report of the result. They should also receive written information to which they may refer later. Information should also be sent to the family primary care physician.
- b) The information should be clear that:
The infant does not have CF.
The baby is a healthy carrier.
Future pregnancies for this couple are not free of risk of CF and the parents may opt for genetic counselling.
There are implications that could affect reproductive decision making for extended family members and the infant when they are of child bearing age.
1.9. What are the minimum acceptable standards for reporting a CF diagnosis following NBS to the family?
- a) A CF Specialist should discuss the result in person with the parents.
- b) The family should receive written information to read after the consultation. The information should also be sent to the family primary care physician.
- c) The family should have a clear understanding of short and long term plans with respect to the child's management.
1.10. What are the minimal acceptable standards for the recognition and management of infants with an equivocal diagnosis
following NBS? Definition; an infant with a repeatedly intermediate sweat test result, or an infant with two CFTR gene mutations (one of which has unclear phenotypic outcome) and a normal or intermediate sweat test result. An intermediate sweat test result is a sweat chloride value between 30 and 59 mmol/L .
- a) The infant should be reviewed by a CF specialist.
- b) This may be in a CF clinic or a non-CF clinic, if local circumstances are appropriate.
- c) Extended gene sequencing should be undertaken when one or no mutations are recognised.
- d) Sweat testing should be repeated in a centre with considerable experience (> 150 sweat tests per annum) and sweat chloride measured by a standard method.
- e) Families should receive clear verbal and written information about the infant and have a clear understanding of what to expect with respect to progress and possible symptoms. Information should also be sent to the family primary care physician.
Isabelle Sermet-Gaudelus (F)
Kevin W. Southern (UK)
Nataliya Kashirskaya (Rus)
It is mandatory to have a high standard of care for diagnostic evaluation in cystic fibrosis. Diagnostic confirmation is required not only for children and adults presenting with suggestive clinical features, but also for infants with a positive newborn screening test or occasionally a positive family history. The following statements refer to a diagnosis outside of newborn screening.
- a) To be able to undertake sweat testing to the standards described below.
- b) To be able to perform genetic testing for the most appropriate panel for the local population. Access to extended exon DNA analysis should be available when required.
- c) Resources to undertake clinical assessment including assessment of respiratory condition (respiratory tract culture for CF-associated pathogens, age appropriate respiratory function testing and imaging), non-invasive evaluation of exocrine pancreatic function and sperm count in male adults.
A sweat chloride above 59 mmol/L
two CF causing CFTR mutations in trans †
at birth or clinical features, including but not restricted to diffuse bronchiectasis; positive sputum cultures for a CF-associated pathogen (especially P. aeruginosa); exocrine pancreatic insufficiency; salt loss syndrome; and obstructive azoospermia (males).
2.3. What are the minimal standards for laboratories performing sweat tests? 
- a) Sweat collection by experienced personnel (at least 150 sweat tests per annum) following national or international guidelines and subject to regular (at least annual) peer review. Internal quality control (usually three samples) of the sweat analysis with acceptable limits of agreement for chloride before each sample.
- b) Use of a commercially available equipment approved for diagnostic use.
- c) A regular external quality assurance for analytes according to national guidelines.
2.4. What are the diagnostic standards of a sweat test? 
- a) The quantity of sweat should indicate an adequate rate of sweat production (15 μL for Macroduct™ tube system).
- b) A sweat chloride value greater than 59 mmol/L is consistent with a diagnosis of CF.
- c) In the first six months of life a sweat chloride value less than 30 mmol/L makes the diagnosis of CF unlikely. There is no international agreement on the lower limit of the borderline range after that age, and thresholds of 30 or 40 mmol/L have been suggested.
- d) Individuals with sweat chloride values in the borderline range should undergo a repeat sweat test and further evaluation in a CF specialist centre, including a detailed clinical assessment and extensive CFTR gene mutation analysis  and .
2.5. What are the minimal standards for a laboratory performing mutation analysis for CFTR? 
- a) The laboratory should be able to perform DNA testing using dried blood spot samples, whole blood (EDTA) and buccal swabs.
- b) Samples should be analysed at least weekly to avoid significant delay in processing.
- c) The laboratory should partake in an external quality assurance exercise with at least an annual certification.
- d) The primary laboratory should be able to provide a limited CFTR mutation panel as a starting point that recognises at least one abnormal allele in more than 90% of the individuals with CF in a local population.
- e) When only one mutation is recognised, an extended exon DNA analysis (gene sequencing) should be available in a primary laboratory or a secondary laboratory.
- f) The disease liability of variants detected by DNA sequencing should be validated against the CFTR2.org database. Novel mutations or variants should be reported to locus specific databases (such as CFTR1 http://www.genet.sickkids.on.ca/app ) in order to facilitate future interpretation of variants of unknown clinical significance.
2.6. What is a CF causing mutation? 
- a) Since CF is an autosomal recessive disease the diagnosis of CF is substantiated in patients who bear two CF causing mutations (classified in the CFTR-2 database) in trans (i.e. one on each homologous chromosome). However, absence of two CF-causing mutations after extended DNA testing in the presence of other typical clinical, laboratory features of the disease or abnormal CFTR bioassays (see below) does not rule out CF.
- b) Patients with “mutations of varying consequence” require further evaluation in a CF specialist centre.
2.7. What are the minimal acceptable standards of care for reporting a diagnosis of CF to a symptomatic patient? 
- a) A positive CF diagnostic test result should be reported promptly (ideally within 24 h).
- b) The patient or parents/carers should receive clear written and verbal information about the disease and be provided with access to electronic media from the health service/national patient organisation. Contact information of the appropriate CF centre should be given (in accordance with treatment pathways for newly diagnosed CF in each country).
- c) Genetic counselling should be offered and contacts for clinical genetic services provided. This will facilitate prevention of CF in affected families, including their relatives who may have an increased risk of the disease.
- d) An early follow-up appointment should be arranged to assess understanding (no more than one week) and contact information of the CF centre should be given.
- e) Patients and parents/carers should receive advice on other information resources, in particular the internet.
- f) At the initial diagnostic meeting patients and parents/carers should receive information about the model for future clinical care.
2.8. What are the minimal standards of care and follow-up for a newly diagnosed patient? 
A patient diagnosed with CF should have immediate access to a CF specialist centre which has the multi-disciplinary capacity to provide care that complies with the ECFS standards of care.
2.9. What are the minimal standards of care and follow-up for patients with symptoms suggestive of CF and intermediate sweat chloride values? and 
- a) A patient in whom the diagnosis is suggestive of CF and an intermediate sweat chloride concentration and only one or no mutation is identified should have access to a CF specialist centre for an appropriate assessment. It is important that such patients have long-term care. Follow-up in a clinic other than a CF clinic may be acceptable in collaboration with a CF specialist centre.
- b) Ancillary tests may help establish a diagnosis of CF by revealing a second organ disease phenotype, such as pancreatic insufficiency (faecal pancreatic elastase), CBAVD in males, lung or sinus involvement, or by identifying an ion channel abnormality (see section 2.10 ).
- c) These patients must be monitored carefully for development of any complications and appropriate therapy implementation.
2.10. Should a patient with equivocal diagnosis have CFTR bioassay tests (nasal potential difference, intestinal current measurement)? 
Patients with a diagnosis that is not clearly CF, should be assessed by a CF specialist. In cases with intermediate sweat test results, further electrophysiological investigations (nasal potential difference, intestinal short circuit current measurement) should be arranged if available.
3. Prevention of progression of lung disease by ensuring all patients have access to therapies of proven effectiveness
Felix Ratjen (Can)
Patrick Flume (USA)
Alan Smyth (UK)
Life expectancy in CF has improved dramatically in the last 4 decades  . However, the majority of CF patients still die of respiratory failure  and so slowing progression of lung disease is a primary aim of CF therapy. The basic defect of CF leads to failure of mucociliary clearance, mucus plugging and secondary infection, with pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. Chronic infection (with neutrophil-driven inflammation) is punctuated by acute exacerbations, following which lung function may fail to return to baseline levels  . Meticulous daily management of lung disease, together with prompt, aggressive treatment of exacerbations are therefore essential to preserve lung function. Best practice in this area is discussed in this section.
3.1. Should initial or new bacterial infection with Pseudomonas aeruginosa be treated?
Left untreated, new infection with P. aeruginosa will progress to chronic infection which is associated with worse lung function, worse nutrition, more pulmonary exacerbations and a higher mortality  . There is no clear evidence how quickly an eradication therapy should be commenced, but treatment should be started promptly (not more than 4 weeks from receiving a positive culture result). There is robust evidence that eradication treatment for P. aeruginosa is effective but no one regimen has yet been shown to be preferred because of superior efficacy  . Options include 28 days of tobramycin solution for inhalation (TIS) and up to 3 months of a combination of nebulised colistin and oral ciprofloxacin  . Follow-up cultures to document eradication after treatment are crucial.
3.2. How should chronic bacterial infection with Pseudomonas aeruginosa be treated?
When eradication therapy has failed, the diagnosis of chronic infection is made and long term inhaled antibiotic therapy should be commenced  . USA guidelines recommend TIS on alternate months for patients over 6 years, with chronic P. aeruginosa, irrespective of the severity of lung disease and continued indefinitely  . Whilst studies are lacking for children younger than 6 years, treatment at equivalent doses is also recommended in this age group. The licenced regimen is 300 mg twice daily for 28 days, alternating with 28 days off treatment. A dry powder inhalation of tobramycin (TOBI PodhalerTM) has been shown to be of equivalent efficacy  . Inhaled aztreonam lysine  is recommended as an alternative by both European and US guidelines. Colistin (2 MU twice daily) is used widely in Europe and is now also available as a dry powder preparation  . A specialist physiotherapist should advise on the timing of inhalational drugs and in an appropriate inhalation technique.
3.3. Is chronic maintenance therapy indicated to treat other bacteria?
Whilst individual patients may benefit from prolonged courses of antibiotics, there is currently little evidence to support chronic maintenance therapy for bacteria other than P. aeruginosa.
3.4. Is prophylactic therapy indicated to treat bacteria?
Prophylactic flucloxacillin for the first years of life to prevent infection with Staphylococcus aureus is endorsed by guidelines in some countries and recommended against in others; its use remains controversial  . There is no evidence to support prophylactic therapy for other bacteria.
3.5. Is physiotherapy an essential component of chronic maintenance therapy and is any form of airway clearance superior to others?
Chest physiotherapy, to achieve airway clearance is advocated in UK  and US  guidelines and should be available to all CF patients. A recent head-to-head trial  has shown that conventional positive expiratory pressure (PEP) is superior to high frequency chest wall oscillation (which relies on expensive equipment). However, in most cases there is little evidence to support the use of one technique over another. The airway clearance technique should therefore be tailored to the individual  . Flexibility and appreciation of patient preference are essential when prescribing a suitable airway clearance technique  . The CF specialist physiotherapist should have a comprehensive knowledge of all techniques: CF pathophysiology, the rationale for alternative approaches and any contraindications to specific treatment techniques  . Exercise and physical activity should be integral to the overall physiotherapy management suggested for every individual with CF, irrespective of age and disease severity. Reduction in exercise capacity is associated with a decline in respiratory function and survival  .
3.6. What are important components of treating patients during episodes of clinical deterioration?
- a) Early recognition and treatment.
Progression of CF lung disease is characterised by periods of stability and intermittent episodes of clinical deterioration, termed pulmonary exacerbations (PEX). There is no agreed definition of a PEX but it is essential that these episodes are diagnosed and treated promptly. Patients having change in their symptoms that could represent a PEX need to have access to a specialised centre without delay. Necessary diagnostic tools for assessment of PEXs include lung function measurements, microbiological testing and radiological tests. Treatment of a PEX usually requires antibiotics which can be administered orally via inhalation or intravenously. If the patient needs hospital admission for intravenous antibiotic therapy it is important that this is not delayed.
- b) Multidisciplinary care.
Treatment of CF exacerbations does not rely on antibiotic therapy alone and requires a multidisciplinary approach. Patients should be reviewed regularly by a specialist physiotherapist who will adjust airway clearance and optimise aerosol regimens where appropriate. Patients often have a reduced appetite and require increased caloric intake during a PEX, due to higher metabolic demands. Access to a specialist dietician is crucial. Intravenous antibiotics should be selected with input from a pharmacist and infectious disease/microbiology specialist.
- c) Antibiotic regimen.
The pharmacokinetics of antibiotics differ between CF and non CF individuals and antibiotic dosages need to be adjusted according to disease specific guidelines (including higher doses in some cases)  . For P. aeruginosa, a combination of two or more antibiotics is recommended and, although evidence is lacking, 14 days of intravenous treatment is routine  . Some patients may benefit from longer therapy and this decision should be based on medical needs rather than resources and costs. Home intravenous antibiotic therapy is used in individual cases, but a home care programme needs to assure that all aspects discussed above are part of the treatment plan. Therefore hospital treatment remains the standard of care for most patients requiring intravenous antibiotic therapy.
- d) Evaluating response to therapy.
It is important to monitor lung function at the beginning and end of treatment of a PEX. Despite intensive treatment about 25% of patients experiencing a PEX requiring intravenous antibiotic therapy will have a persisting decline in lung function  , emphasising the need for maintenance therapies to prevent exacerbations.
3.7. What are the recommended chronic maintenance therapies to maintain lung health?
A comprehensive review of this topic is beyond the scope of this document and is available elsewhere  and . Airway clearance techniques, physical activity and nutritional support are important components in maintaining lung health; here we focus on drug therapy only.
The only mucus degrading agent that has proven efficacy in CF is dornase alfa. Studies have demonstrated improvements in lung function and a reduction in pulmonary exacerbations in patients regardless of disease severity  . Recent evidence from an analysis of a large data base suggests that dornase alfa reduces lung function decline  . Treatment effects are lost when treatment is ceased, therefore long term maintenance therapy is required. Other mucolytics, such as N acetyl cysteine, have not been proven to be effective in CF patients  .
3.7.2. Hydrator therapy
Airways in CF are dehydrated and increasing the airway surface liquid can be accomplished with osmotic agents that are called hydrators. The mechanism of action differs from that of dornase alfa and both approaches are complimentary. Hypertonic saline and mannitol are available as inhaled agents in Europe. Hypertonic saline (7%) has been shown to reduce pulmonary exacerbations and marginally improve lung function in a systematic review  . H ypertonic saline is currently used in many patients with moderate to severe lung disease and is supported by guidelines  . Mannitol has been introduced more recently and improves lung function  and . The drug is available as a dry powder formulation thereby reducing treatment time. Both agents act as irritants and require pre-treatment with a bronchodilator and initial tolerability testing.
3.7.3. Antibiotic therapy
Airway infection in CF can be divided into early, intermittent and chronic infection. This scheme has been useful for P. aeruginosa infection (see question 1 above) and may also apply to other bacteria. If eradication fails and chronic infection with P. aeruginosa develops, inhaled antibiotic therapy has proven efficacy to reduce pulmonary exacerbations, improve lung function and respiratory symptoms  and is therefore part of standard of care  and . Inhaled antibiotic therapy should be administered as long term maintenance therapy with either single agent therapy or alternating therapy of different antibiotics. The benefits of treatment outweigh the risks associated with the development of antimicrobial resistance which is often overcome by high topical antibiotic concentrations.
Macrolides are beneficial to CF patients likely due to their dual effect on infection and inflammation. Whilst not primarily efficacious against P. aeruginosa, there is evidence suggesting efficacy if the organism resides in biofilms which is the case in chronic P. aeruginosa infection. Maintenance therapy with azithromycin has been shown to improve lung function and reduce PEXs in chronically infected patients  and is part of recommended care  . A reduction in pulmonary exacerbations has also been observed in younger patients not infected with P. aeruginosa  . Some concerns remain, regarding the durability of their effect and their impact on inducing resistance for other bacteria.
3.8. Is airway inflammation a target of chronic maintenance therapy and how should it be treated?
Inflammation is an important component of CF lung disease. CF airway inflammation is neutrophil dominated and common anti-inflammatory drugs such as corticosteroids, either systemic or inhaled have no proven efficacy in CF patients, outside of treatment of concomitant asthma. High dose ibuprofen has been shown to reduce lung function decline  . Treatment requires monitoring of drug levels and despite these promising data it has not received widespread acceptance. Whilst other anti-inflammatory therapies are currently being studied, they are neither supported by sufficient evidence nor available for clinical care at the present time.
3.9. CFTR modulator therapy — which treatments address the underlying defect in CF?
Current treatment largely addresses the symptoms caused by the defective gene whilst CFTR pharmacotherapy aims to increase protein expression at the cell surface, or its function, with drug therapy. This treatment strategy could make a major difference in altering or even halting the disease process. Different drugs targeting specific classes of CFTR defects are currently being studied; to date only one drug has clearly demonstrated clinical efficacy. Ivacaftor, a CFTR potentiator studied in the gating mutation G551D, not only enhanced ion transport reflected by reductions in sweat chloride concentrations but also improved clinical measures such as lung function and PEXs  . The effect size of lung function changes exceeded that observed for any drug therapy available for CF patients to date. Whilst this mutation is found in less than 5% of patients worldwide, ivacaftor is a proof of principle demonstrating the potential impact of CFTR pharmacotherapy. In patients with the G551D mutation ivacaftor should be part of standard of care.
3.10. How should fungal infections and severe/recurrent Allergic Bronchopulmonary Aspergillosis (ABPA) be treated?
Aspergillus fumigatus as well as other fungi are commonly found in sputum of CF patients. Whilst their relevance is not entirely clear, more recent evidence suggests that A. fumigatus may act as a pathogen in at least in some CF patients  . Sputum cultures in CF patients should therefore include assessments for fungi. Allergic bronchopulmonary aspergillosis is a well characterised complication in CF patients and should be considered in any patient with clinical deterioration not responding to antibiotic therapy  . Diagnostic tests include allergy skin testing, measurements of serum IgE and IgE specific to Aspergillus, and serum precipitins for Aspergillus. These tests need to be available to every CF care facility. Treatment is with oral prednisolone plus/minus antifungal therapy  .
3.11. How should we monitor lung disease?
- A multi-disciplinary team is needed to assess and discuss all aspects of CF care.
- Regular monitoring includes assessment of competence of airway clearance and inhalation technique and monitoring of adherence.
- Clinical assessments that should be performed at least every 3 months and at times of symptomatic deterioration  .
- As airway infection is a major driver of CF lung disease airway cultures should be obtained at every clinic visit  . The microbiological assessment needs to include specific culture media for the range of CF pathogens to ensure that relevant organisms are not overlooked.
- Lung function testing guides therapy and should be performed at every clinic visit in patients old enough to cooperate (usually 5 years and older)  . Tests for younger children are currently under development. Routine lung function testing should include spirometry performed according to ATS/ERS criteria  and testing pre and post bronchodilator should be available.
Chest X-rays are routinely performed on an annual basis in most CF centres as well as at times of clinical deterioration. Other imaging modalities such as high resolution CT scanning should be available as well and are used routinely in some CF centres.
4. Optimal nutrition and management of metabolic complications of cystic fibrosis
Anne Munck (F)
Sarah Jane Schwarzenberg (US)
Sue Wolfe (UK)
Nutritional status has a strong positive association with pulmonary function and survival in CF. Attainment of normal growth in children and maintenance of adequate nutrition in adulthood represent major goals for the CF team.
4.1. What are the goals for nutritional status in patients with CF?
Infants and children should grow normally, with infants achieving normal weight and height percentiles similar to the non-CF population by two years of age. Older children and adolescents should achieve the 50th percentile for body mass index (BMI). In adults absolute BMI should be maintained above 20 kg/m2, ideally, 22 kg/m2 (females) and 23 kg/m2 (males). All patients should have normal fat soluble vitamin and micronutrient status. Essential fatty acid status should be monitored, if the assay is available. Guidelines have been published on nutritional evaluation and management , , , , , , , , and .
4.2. How do we monitor nutritional status in routine care?
Until growth ceases, accurate measurement of weight (kg), length or height (m), and head circumference (cm) (up to 2 years of age) should be made at each hospital visit. In adults, height should be measured annually. Measurements should be converted to BMI (> 2 years) and compared to national reference charts. Special attention is needed for toddlers and adolescents due to rapid growth velocity , , , , , , , , , , and .
4.3. How do we determine exocrine pancreatic insufficiency (EPI) and adequate pancreatic enzyme replacement?
Confirmation of EPI is required. Coefficient of fat absorption (CFA) is the “gold standard”, but is cumbersome. Faecal pancreatic elastase-1 (FE1) is simple and reliable from two weeks of age in the absence of liquid stools.
Pancreatic sufficient patients should be monitored by annual FE1 during infancy and childhood and during periods of failure to thrive, weight loss or diarrhoea.
Pancreatic enzyme replacement therapy (PERT) adequacy is determined clinically, monitoring nutritional status, signs and symptoms of malabsorption and excessive appetite with poor weight gain. Inappropriate doses of PERT may result in abdominal pain and constipation.
4.4. What are the main strategies to providing preventive nutritional care?
CF centres should be familiar with the recommendations for age-appropriate dietetic advice directed by CF dietitians , , , , , , , , , , , , and . This includes:
- Assessment of EPI and administration of PERT.
- Selection of appropriate diet, with attention to a high fat intake.
- Behavioural therapy to achieve positive mealtime experiences.
- Providing sodium supplementation, when necessary, with special awareness in newborn screened infants.
- Supplementing fat soluble vitamins, as indicated by laboratory testing.
Women with CF who plan their pregnancies should receive pre-conception advice to improve their nutritional status  .
4.5. What factors should be evaluated in patients with poor growth?
Evaluation should be triggered by weight loss, or decline in weight or length/height percentile (< 2 years of age), or decline in BMI percentile for age and gender (> 2 years of age), or poor linear growth (< 18 years) or decline in BMI (> 18 years). Early intervention is essential to avoid significant loss of weight or growth.
Diagnosing the cause of malnutrition relies on a careful assessment and a multidisciplinary approach. Potential causes include insufficient food intake, excessive stool energy losses (inadequate PERT or poor adherence), Giardia infection, coeliac disease, hypercatabolism from pulmonary disease, vomiting or gastroparesis, glycosuria and psychological impacts of CF.
4.6. What are the options for interventional nutritional care?
Interventions should be tried stepwise for a limited period of time or until nutritional status is optimised, depending on the severity of malnutrition and the age of the patient.
- Anticipatory guidance. Reinforcement of adherence to diet, sodium and enzyme recommendations, using behavioural modification or motivational interviewing
- Moderate malnutrition. Oral supplements should be used as additional calories in a time-limited trial or temporarily as meal replacement for ill patients. Temporary nasogastric (NG)/nasojejunal (NJ) feeds may be useful
- Severe malnutrition. Enteral feeding via NG or gastrostomy tubes usually improves and maintains nutrition in a patient with CF
Other therapies: Cyproheptadine and growth hormone are not part of routine management. Parenteral nutrition is only appropriate when enteral nutrition is impossible or fails.
Nutritional rehabilitation can take 3–6 months, so if being used pre-operatively should start well ahead of an anticipated operation (e.g. organ transplantation) , , , , , and .
4.7. When and how do we screen for diabetes mellitus?
All CF patients who have not been diagnosed with diabetes/CFRD including those who may have had gestational diabetes should be screened during a period of clinical stability using the standard WHO protocol annually from age 10 years. A single abnormal OGTT requires confirmation with a second test. Refer to the published guidelines for additional detail.
Published guidelines , , and  suggest more frequent screening with fasting/post-prandial glucose and/or OGTT in the following situations: pulmonary exacerbation, initiation of glucocorticoids, enteral tube feeding, planning for pregnancy, during pregnancy, planned organ transplantation and where there are symptoms of diabetes.
4.8. What is the current management of CFRD?
Patients with CFRD require care from a multi-disciplinary management team with experience in CFRD and in communication and consultation with the CF team. It is recommended that CFRD be treated with insulin, not oral diabetic agents. Glucose control may be challenging during pulmonary exacerbations, requiring more frequent monitoring and increased insulin. CF nutritional guidelines apply to CFRD patients. Modification of calorie, fat, protein, or salt intake as a result of the diagnosis of diabetes is not appropriate. Monitoring for complications of CFRD is similar to that for other forms of diabetes. CF patients with impaired glucose tolerance (IGT) must be monitored closely, particularly when ill, as they may need insulin therapy intermittently.
4.9. Should patients be screened for CF bone disease and if so, how and which factors are involved in the prevention of reduced bone mineral density?
Low bone mineral density (BMD) is a common complication in adolescent and adult patients and can occur in children as clinical status declines. Routine screening for reduced BMD using dual energy X-ray absorptiometry (DXA) scans from the age of eight to ten years is recommended, as detailed in published guidelines , , and .
Centres should be familiar with the factors contributing to development of reduced BMD in CF and how to reduce these risks. The most common risk factors include: pulmonary infections, poor nutritional status and lack of weight bearing exercise, delayed puberty, glucocorticoid treatment, hypogonadism, and vitamin D, calcium and vitamin K deficiencies , , and .
4.10. What is the current management of reduced bone mineral density?
Known risk factors should be minimised and dietary intake of calcium and vitamin D should be optimised to enhance bone health. The use of bisphosphonates should be considered on an individual basis, taking bone mineral density, low trauma fracture history and transplant status into consideration , , and .
5. Treatment of the complications of cystic fibrosis in a timely and effective way
Patrick Flume (USA)
Giovanni Taccetti (It)
Alan Smyth (UK)
5.1. Pulmonary complications
Patients with cystic fibrosis (CF) may develop a variety of complications which, although infrequent, occur commonly enough that the CF centre should be well-prepared in their management. The following offers standards of diagnosis and management for these complications as well as resources for additional guidance.
5.1.1. What is the best way to manage pneumothorax in patients with CF?
Pneumothorax is a complication occurring more commonly in patients with more severe obstructive airways disease  . The CF centre should have a high suspicion for this complication in the patient with acute chest pain and shortness of breath and be able to make the diagnosis using radiologic studies (i.e. chest X-ray, CT chest). Management guidelines have been published  ; the Centre should be able to provide basic treatment (i.e. chest tube, pain control). For those patients who may need more complicated procedures (e.g. VATS), the Centre should have pre-agreed referral process with Thoracic Surgery Services.
5.1.2. What is the best way to manage hemoptysis in patients with CF?
Hemoptysis is a common complication and may range in severity from scant to massive, defined as > 240 ml/day or > 100 ml/day for several days  . Management guidelines have been published  . The Centre should give the patient and family clear guidance about when to call, if hemoptysis occurs, and should be able to provide the recommended therapies. For severe bleeding, the Centre should have access to interventional radiology (e.g. bronchial artery embolisation) and/or thoracic surgery.
5.1.3. What is the best way to manage respiratory failure in patients with CF?
The natural history CF lung disease is progression to advanced stage airways obstruction and eventual respiratory failure. The Centre should recognize progression to this stage and have discussions about lung transplant and advanced healthcare directives (see Section 6 ). The need for supplemental oxygen should be assessed in the patient with advanced stage lung disease (FEV1 < 40% predicted) both at rest and with exercise  . Ventilatory support (e.g. non-invasive ventilation) should be provided in accordance with the patient's wishes for palliation of dyspnea  . The Centre should be able to assess the need for opiates to relieve dyspnea and pain associated with advanced stage disease  and .
5.2. Liver and pancreas complications
5.2.1. What is the best way to manage liver disease in patients with CF?
Many pancreatic insufficient (PI) CF patients will have evidence of liver disease ranging in severity from very mild biliary fibrosis to end-stage cirrhosis. Cystic fibrosis related liver disease (CFLD) is a biliary cirrhosis that usually presents before age 20 years and can lead to portal hypertension and hepatic failure  and . The Centre should monitor all patients with routine physical examination and periodic liver enzyme testing. Guidelines on the use of ultrasonography, ursodeoxycholic acid (“Urso”), and when to consider a liver biopsy, are available in published guidelines , , and .
Patients with portal hypertension should be referred to a gastroenterologist/hepatologist for screening endoscopy and management of complications of pulmonary hypertension. Routine management of CF patients with cirrhosis should include immunisation against hepatitis A and B viruses, avoidance of NSAIDs and hepatotoxic agents (e.g. alcohol), and monitoring of the functional status of the liver (i.e. coagulation, albumin). The Centre should have a pathway for referral to a liver transplant programme, for those patients with advanced stage liver disease.
5.2.2. What is the best way to manage cholelithiasis in patients with CF?
Cholelithiasis is not always symptomatic  . The Centre should be suspicious when evaluating the patient with nonspecific abdominal pain and nausea. The Centre should have access to ultrasonography and HIDA scan for assessment of the gallbladder. For symptomatic gall stones, ursodeoxycholic acid is ineffective and surgical referral is usually necessary.
5.2.3. What is the best way to manage pancreatitis in patients with CF?
Pancreatitis is a less common complication in the CF population, but troublesome in some CF individuals with pancreatic sufficiency  . Recurrent acute pancreatitis may contribute to the transition from pancreatic sufficiency to insufficiency in CF. The presentation may be a nonspecific abdominal pain, so there should be a high suspicion when seeing a patient with a recurrent, unexplained pain and associated nausea and vomiting. The Centre must be able to evaluate with standard laboratory testing (i.e. amylase, lipase) and imaging (e.g. ultrasonography, CT, or MRI). Management principles are not different than for non-CF pancreatitis. However, acute pancreatitis is associated with severe dehydration and in the CF population, this may be more severe and attention to rehydration and electrolyte monitoring is crucial.
5.3. Gastrointestinal complications
5.3.1. What is the best way to manage gastroesophageal reflux disease (GORD) in patients with CF?
GORD occurs commonly in patients with CF, affecting approximately 30%  . The Centre should be aware of the signs and symptoms of GORD and be able to provide appropriate diagnostic testing (i.e. impedance and pH probe, upper endoscopy) and treatment  .
5.3.2. What is the best way to manage constipation in patients with CF?
Constipation has a slow onset with reduced stool frequency  . It is common in CF and may be exacerbated by the use of narcotics. Most of the time constipation responds to hydration therapy, stool softeners (e.g., polyethylene glycol) or laxatives  . Enemas are rarely needed.
5.3.3. What is the best way to recognize and manage distal intestinal obstruction syndrome (DIOS)?
The symptoms of DIOS have acute onset with right lower quadrant pain  . The Centre should be able to recognise this complication (and its variants) and have standard protocols for diagnosis and treatment based upon published recommendations , , and . Patients may respond to oral rehydration combined with stool softeners, but more severe cases may require IV hydration, nasogastric aspiration, and enemas. For patients who fail such conservative therapies, referral to a gastroenterologist with knowledge of DIOS is essential. Surgical intervention should be considered only in extreme situations and so the Centre should have surgeons who know about the gastrointestinal complications of CF.
5.3.4. What is the best way to prevent fibrosing colonopathy (FC)?
This is an uncommon complication. The only clear recommendation to prevent FC is to use the appropriate dose of pancreatic enzymes, not increase enzyme dose without clear indication and not exceed 10,000 lipase units/kg/day total enzyme dose  .
5.3.5. What is the best treatment for appendiceal mucocele?
Ultrasonography will aid the diagnosis  . In case of symptoms, appendectomy with resection of the appendix edges and resection of the caecal tip will avoid risk of recurrence.
5.3.6. What is the best way to manage small bowel overgrowth in patients with CF?
Small bowel overgrowth is suspected when patients have diffuse or periumbilical abdominal pain, excessive bowel gas, nausea, and malabsorption despite adequate enzyme intake. Risk is higher in patients who have had previous intestinal surgery or are using narcotics. It is recommended that diagnosis be made by clinical therapeutic trial of metronidazole  . An opinion from a gastroenterologist is essential.
5.3.7. What is the best way to manage meconium ileus (MI) in patients with CF?
MI is a neonatal emergency best handled by a pediatric surgeon (and pediatric radiologist) with expertise in MI, who should liaise promptly with the CF centre. The surgical team should be familiar with both non-surgical and surgical management  and . Complicated MI is more severe, more difficult to treat, and may require prolonged hospitalisation. Post-operative management may require a centre familiar with nutritional management of short bowel syndrome.
5.4. Other complications
5.4.1. What is the best way to manage medication toxicities?
The treatment of CF lung disease can result in complications due to the treatment and toxicity related to medications, especially aminoglycosides (e.g. nephro-, oto-, and vestibular toxicity).
The Centre should utilise standard protocols for therapeutic drug monitoring when using aminoglycosides following recommended treatment dosing  . There should be strict avoidance of NSAIDs when using intravenous (IV) aminoglycosides to avoid nephrotoxicity. The Centre should perform assessment for ototoxicity using audiology testing for patients who have hearing loss or tinnitus, or as part of a routine screening assessment. The Centre should have access to a clinician experienced in vestibular assessment.
5.4.2. What is the best way to manage nephrolithiasis in patients with CF?
Nephrolithiasis is common in CF patients  . The Centre should be aware of the signs and symptoms associated with nephrolithiasis and able to evaluate by urinalysis and CT-IVP. The metabolic disorder causing kidney stones should be determined. The Centre should have access to a urology specialist and interventional radiologist for complicated nephrolithiasis.
5.4.3. What is the best way to manage arthropathy in patients with CF?
Arthralgias are common symptoms in CF patients  but arthropathy remains poorly understood. The Centre should be aware of this problem and have access to a rheumatologist who has knowledge of CF.
5.4.4. What is the best way to manage sinus disease in patients with CF?
Chronic sinusitis with or without nasal polyposis is common in patients with CF  . The Centre should routinely evaluate sinus disease and offer a recommended treatment, recognizing that this could be a source for lower airways infection  . The Centre should have access to diagnostic testing (i.e. CT sinus) and to an otolaryngologist experienced with CF-related sinus disease.
5.4.5. What is the best way to manage allergic disease in patients with CF?
With the exception of ABPA, discussed elsewhere in this document, the prevalence of allergic disease is not increased in CF patients and can be managed as for the general community. However patients can develop drug allergies (e.g. antibiotics) that can complicate treatment decisions. The Centre should be aware of the signs and symptoms of possible allergic response to treatment and should know when to stop that therapy accordingly. The Centre should have established protocols for desensitisation.
5.4.6. What is the best way to avoid complications that result from chronic indwelling intravenous (IV) catheters in patients with CF?
An indwelling IV catheter should be placed in accordance with the patient's wishes if difficulties exist in performing IV treatment. The Centre should have access to professionals experienced in the placement of indwelling catheters (e.g. Port-A-Cath). Only trained individuals should access the indwelling catheter, using standardized protocols in infection control and maintenance of the catheter. Common complications of catheters include vascular problems (e.g. infection, thrombus, SVC syndrome)  and . The Centre should have a keen awareness of the signs and symptoms of catheter-related complications and be able to perform proper testing including blood cultures (to assess for infection), ultrasonography and contrast radiology studies (CT or MRI) for vascular occlusion.
5.4.7. What is the best way to address pregnancy in a CF patient?
Pregnancy can complicate the management of women with CF. The Centre should always inquire about possible pregnancy when assessing women who may be fertile, especially when considering additional medications that are contraindicated in pregnancy. The pregnant CF patient should always be considered as having high-risk pregnancy because of the potential pulmonary and nutritional/metabolic complications and should be seen by an obstetrician experienced in high-risk cases. Management recommendations for pregnant CF patients have been published  .
5.4.8. What is the best way to address infertility in a CF patient?
Females with CF can become pregnant and those with good lung function and nutrition are likely to complete the pregnancy. In less well females there is the possibility of reduced fertility, and they should be referred to specialists in fertility services if there is a perceived inability to become pregnant. Most (98%) CF males will be azoospermic and should be informed of this finding at an appropriate age. Sperm analysis should be offered to those patients interested in knowing their status. Patients should receive proper counselling regarding fertility options including assisted reproductive techniques.
6. Transplantation and appropriate management of end of life issues
Scott Bell (Aus)
Alistair Duff (UK)
Transplantation is an established therapy for end-stage lung and liver disease in patients with CF. Referral to transplant services is enhanced by the CF team having an understanding of the processes leading to a success transplant. In some patients, transplant is not a suitable treatment option or does not occur. Effective management of the end of life is vital and requires attention to communication, symptom control and a multi-disciplinary approach to care, including expertise in palliative care. These standards include a series of questions about the approach to transplantation assessment and end of life care, utilising available published evidence and published transplant guidelines. For a detailed review of all facets of the topic see “Practical guidelines: Lung transplantation in patients with cystic fibrosis” prepared by the European Centres of Reference Network for Cystic Fibrosis (ECORN-CF) Study Group  and the ECFS End of Life Care Guidelines  .
6.2.1. What are the important determinants for the timing of listing for lung transplantation in patients with CF?
The lead time for assessment and waiting for suitable donor lungs is variable but can be in excess of two years. Factors that are associated with increased mortality  and  and where transplantation referral  is recommended are in patients with:
- FEV1% predicted of ≤ 30% predicted,
- Rapid decline, particularly female and younger patients,
- Oxygen therapy for hypoxaemia,
- Frequent exacerbation that responds poorly to intravenous antibiotics.
Earlier referral should be considered in patients with refractory pneumothorax and recurrent massive haemoptysis  . Increased survival, limited donor availability and differences in organ allocation schemes have led to prediction models of mortality/survival which assist with decisions for prioritising patients for transplantation  and . The complexities of timing transplantation-referral require close liaison with the Transplant Service. This will also help patients process complex information and make informed choices.
6.2.2. What clinical features increase the risk for dying on the lung transplant waiting list?
- Oxygen-dependent respiratory failure,
- Chronic hypercapnia,
- Pulmonary hypertension,
- Undernutrition, especially female patients.
The limited donor pool determines the number of possible transplants. National policies optimise the efficiency of donor-organ allocation differently, depending on donor identification systems and practical/geographical logistics. Prioritisation of urgent cases is managed at a national level.
Regular and detailed communication with the Transplant Service is vital to allow regular updates of the clinical progress of all wait-listed patients.
6.2.3. What are the important patient variables, which may prevent active listing for lung transplantation in CF?
Exclusions for lung transplantation  include:
- Malignancy within 2 years. A disease-free period of 5 years is generally required. Consideration for cutaneous and some urogenital cancers may be given
- Untreatable dysfunction of another major organ (e.g. heart, liver, kidney),
- Chronic extra-pulmonary infection (e.g. hepatitis B, hepatitis C, HIV),
- Severe skeletal deformity,
- Prolonged poor-adherence or irregular clinic attendance,
- Untreatable psychological condition/s limiting ability to participate with therapies,
- Lack of consistent social support system,
- Substance addiction (e.g. alcohol, tobacco, within previous 6 months).
Most transplant services do not assess patients with:
- Chronic Burkholderia cenocepacia
- Mycobacteria abscessus.
Other infections (e.g. multi-resistant Pseudomonas aeruginosa, Scedorsporium species, Clostridium difficile) are influenced by local transplant unit policy and experience and require detailed discussion.
Combined ‘liver/lung’ or ‘lung only’ transplantations require careful consideration in patients with advanced lung disease and portal hypertension.
6.2.4. What complications of CF are important to prioritise prior to lung transplantation?
Optimising nutritional status is a priority for wait-listed patients, but should not be a strong factor in delaying the listing process  .
CFRD is present in 40–50% of patients at assessment and develops post transplant in another ~ 20% of patients. Increased mortality, infection and rejection-related hospitalisation have been reported in patients with CFRD at transplantation. Optimising control of CFRD is important whilst wait-listed  and .
Chronic kidney disease (CKD) occurs in many adults with CF and where practical, limiting exposure to nephrotoxic drugs pre-transplant should be considered  . The impact of long-term systemic use of aminoglycosides before transplantation on post-transplant renal function is uncertain  . Calcineurin inhibitors, hypertension and CFRD have been associated with CKD following transplantation.
Osteoporosis (24%) and osteopenia (38%) is reported in patients with CF  . Biphosphonate therapy may be required to maintain and improve bone health pre-transplantation.
Systemic corticosteroids are required in some patients with advanced lung disease (e.g. APBA). Limiting daily dose of prednisolone to < 15 mg/day will assist in healing and reduce post-operative infection risk and limit further reduction in bone density.
Psychologically it is vital to help patients maintain hope and counter demoralisation or exhaustion.
6.2.5. Under what circumstances should invasive ventilation be considered in patients with CF?
The role of invasive ventilation for patients with end-stage pulmonary disease is controversial and associated with poor outcomes  .
Consideration should be made for patients who develop respiratory failure in the setting of an acute precipitant and where recovery is anticipated (e.g. massive haemoptysis, pneumothorax, influenza, post-operative care)  and .
Transplantation from the ventilator is associated with higher early mortality  and is only offered in highly selected cases and not by all transplant services. Usually this only occurs in patients who have completed transplant work-up prior to ventilation.
Some transplant services consider transplantation in patients who have required Extracorporeal Membrane Oxygenation (ECMO) for severe respiratory failure. Case reports have suggested excellent outcomes  . Close communication between the CF Team and the Transplant Service is mandatory prior to ECMO initiation.
6.2.6. What therapeutic modalities are important in the palliative care of the patient with CF?
Early discussions (including the potential for transplantation) to allow time to psychologically adjust and carefully consider options is required, particularly as misunderstanding is common. The physician should initiate a conversation about end of life care with the patient and family and should involve the multidisciplinary team. Significant psychological intervention can be required (e.g., management of anticipatory grief and work with family members)  .
Symptoms that frequently require control include dyspnoea, chest pain, headaches, fatigue and poor sleep quality  . The use of narcotic analgesic, anxiolytics, airway clearance support, psychological strategies, oxygen and non-invasive ventilation support are important  . Teams should access support from palliative care colleagues to optimise symptom control, when required  and .
The balance between effective active treatments whilst providing adequate symptom control can be difficult especially in patients waiting for transplant  and . Symptom control does not preclude lung transplantation, however close communication between CF and Transplant teams is vital  .
The death of a patient can have a significant effect on other patients and staff at the centre. Support of other patients with CF and staff members should be offered  .
6.2.7. What factors are important in deciding on the location of care for the dying person with CF?
Patients' and families' wishes should be the key to making decisions about where to manage the dying patient and where practical, measures taken to assist facilitating these wishes. The support available at home to optimally manage all symptoms is a key consideration (e.g., providing airway clearance support, the availability of timely symptom control).
Active management of patients to maximise symptom control often continues and potential for conflict between active management and optimising control symptoms needs to be carefully considered.
Communication between all team members, community healthcare team (including primary care), the patient and the family are vital.
6.2.8. How should CF-specific complications be managed following recovery from lung transplantation?
After lung transplant, management of complications of CF remains important (e.g. CFRD, osteoporosis, DIOS). In many cases, the transplant service manages the complete care of the patient. However, the CF Centre should be available to support where assistance is desired.
Psychosocial input is required to address psychopathology (e.g. drug-related psychosis, post-traumatic stress reactions).
7. Psychosocial support
Alistair Duff (UK)
Gerald Ullrich (Ger)
Mandy Bryon (UK)
Living with CF can be emotionally and physically challenging for the patient with CF and their relatives. The condition and its treatment influence the ability to deal with normal tasks of daily living and unexpected life events. Good psychosocial care is now well-integrated into the medical team and there is a substantial body of literature that establishes the essential elements of the psychosocial role  and . The focus of this paper is to prioritise key psychosocial issues and make recommendations for appropriate management.
7.1. What are the core elements of supporting parents in the first year, post-diagnosis?
Diagnosis of CF for the majority is by newborn screening. Screening for CF aims to minimise morbidity and mortality, yet potential disadvantages must be recognised and effects minimised  . Diagnosis of CF is traumatic, especially in an otherwise healthy infant. Parents can experience disbelief and dissociation from the diagnosis and baby, which can last well beyond the first few weeks  . Preventative counselling and emotional support must be offered to assess parents' (i) understanding of information, (ii) reactions to diagnosis and, (iii) coping style, support needs and resources.
Parents need to engage in education about their child growing up with CF, ensuring balance between managing a complex health condition and enabling their child to grow with good self-esteem and concept. Families should be hopeful that their child will enter adulthood having a good quality of life with achievements similar to non-CF peers.
Key tasks are to advise on:
- Establishing treatment with baby's daily-routine
- Helping parents accept and administer treatment
- Communicating to family and friends about the medical condition
- The availability of psychosocial follow-up for parents if required including couple counselling
- Available financial support/benefits/allowances and other sources of support.
7.2. International Depression/Anxiety Epidemiology Study (TIDES)
European data emerging from the International Depression/Anxiety Epidemiology Study (TIDES) show that elevated depression scores are no different to general populations although higher anxiety scores have been reported, particularly amongst women. Several risk factors have emerged for increased depression and anxiety scores amongst patients. Anxiety and depression also appear particularly problematic in parents. Support for these problems should be available from the CF service. In what ways should they be identified and addressed?
The CF team needs to assess the psychological well-being of people with CF routinely (see Centre Framework for access to psychological professionals). Surveillance for depression and anxiety in patients and parents should be conducted during annual review with psychometrics (e.g. HADS, CES-D) or discussion.
Elevated psychometric scores require diagnostic confirmation. This should be undertaken by the CF Team psychologist via clinical interview. Where there is no integrated psychologist, referral should be considered to mental health agencies.
Psychological intervention when required, needs to be supported with consideration of the practical, social, educational and vocational needs of the patient and their caregivers.
7.3. How do we promote psychosocial resilience at key transition points and address potential associated psychosocial vulnerability?
Transitions relate to significant changes in developmental and personal prospects and challenges for people with CF and the sense of responsibility these imply.
Key transition points are:
- i. Parental adaptation to diagnosis
- ii. Commencement of schooling; nursery, primary and secondary
- iii. Parental- to self-guided treatment
- iv. Transition of care from paediatric to adult services
- v. Entering the workplace or further education
- vi. Loss of independence (e.g. retirement, loss of activities and functioning, increased reliance on intrusive treatments and carers, and facing transplantation or end of life).
Psychosocial resilience is broadly an ability to recover from negative events with an absence of lasting emotional disturbance. It is multi-factorial, the elements of which are not all amenable to change  . The primary focus should be to increase social support and foster hope (primarily by paediatric preparation of patients for fulfilling adult lives and increasing self-efficacy and control). Emotional vulnerability should be addressed pro-actively at each transition point.
7.4. What are the core components in addressing adherence, particularly to nebulised therapies?
Improving adherence, particularly to nebulisers, is a key challenge for the prevention of progression of disease. Successful psychosocial intervention is determined by: (i) the Team ethos to patient care, (ii) collaboration with patients to increase their motivation and (iii) identifying barriers and actively supporting patients' efforts to increase treatment.
- i. Teams must endorse a collaborative, nurturing and holistic approach to adherence, based on effective information-giving and empathic communication. Open discussion leads to facilitating care that is individually meaningful and accounts for needs for involvement and making informed choice. Psycho-social professionals need to support team-members' efforts to engage patients in conversation using active-listening skills
- ii. Persuading patients with chronic sub-optimal adherence does not work. Psychosocial professionals must lead on efforts to address perceptual or emotional barriers to adherence in patients unwilling to acknowledge problems or who lack motivation 
- iii. A range of psychological strategies are effective (e.g., reinforcement scheduling, problem-solving). Clinical trials of interventions are ongoing. Psychosocial professionals must achieve competence and provide leadership about techniques.
7.5. What are the main components to supporting patients diagnosed in adolescence/adulthood?
CF diagnosed beyond childhood may be for a range of reasons, mild or mis-diagnosed symptoms or less severe phenotype  . Patients often are angry and overwhelmed by information (prognosis, infertility) and ‘technical’ aspects of busy CF clinics. This leads to challenges in building a trusting alliance. A flexible and individualised approach to clinical management is needed for the particular patient which differs from the routine care provided to those diagnosed in early childhood. Emphasis must be placed on prognosis, fertility issues, personal support, and reviewing what CF knowledge patients may have acquired and from where (some sources being misleading)  .
7.6. Disordered eating and body image problems in patients impact on treatment and prognosis. What are the key components in addressing these?
Competing demands from CF management including monitoring of nutritional status emphasising weight gain within a culture emphasising thinness contribute to confused attitudes towards eating. Disordered eating and body image problems have been reported in people with CF  .
The approach to nutritional management needs to take account of the patient's attitudes towards eating, shape and personal appearance, rather than focus simply on calorie intake and weight gain. Assessment of nutritional intake should include questions on the above and diet plans incorporating healthy eating idea.
Educational programmes should be available to inform people with CF about digestion, calorie consumption and energy usage in CF. Health professionals working with people with CF should be equipped to identify disturbed eating behaviours allowing early detection and joint intervention between dietitian and psychologist is recommended.
7.7. How should we tackle the key psychosocial issues of adulthood and growing older with CF?
Key issues of adulthood are (i) normal tasks of adulthood being made more complex due to CF, (ii) making complex decisions (e.g. making vocational plans or making treatment decisions) and, (iii) coping with deterioration in health and loss of mobility and independence, as well as new complications diagnoses (e.g., CFRD), that can lead to, for example, increased anxiety and depression (demoralisation), low self-esteem and relationship difficulties.
Key approaches are:
- i. A pro-active approach during routine clinics and assessment during annual review can help identify emotional, practical and social support requirements (e.g., employment, fertility, risk-taking behaviours). Patients tend not to initiate these  and 
- ii. Referral to a CF team's psychosocial professional or external specialist mental health services.
CF teams must be aware of the likelihood of demoralisation occurring as a consequence of multiple health problems. This resembles, but is different from, depression in personal impact and treatment  .
7.8. What are the core aspects of training and supporting the MDT in developing psychosocial skills?
All members of the Team need to have some psychosocial skills. A 4-step skills model is described;
- i. Team members should have training to enable recognition of psychological needs and provide information and general psychological support. Be able to access psychiatric services in an emergency.
- ii. A team member can have additional training to: enable screening and referral for psychological distress, administer psychological first-aid following traumatic medical events (e.g., haemoptysis) and implement particular psychological techniques (e.g., desensitisation to painful procedures).
- iii. Trained and accredited team member to assess for psychological distress and implement specific therapeutic techniques (e.g. counselling or therapy delivered according to an explicit framework). Requires supervision from a qualified mental health trained professional.
- iv. Qualified mental health specialist (e.g. clinical psychologist), who can diagnose psychopathology and treat using specialist psychological interventions.
Conflict of interest
A.R. Smyth: personal fees from Gilead, other from MPEX, other from Pharmaxis, other from Vertex, grants from Forest Labs, outside the submitted work; S.C. Bell: grants and non-financial support from Vertex Pharmaceuticals, personal fees and other from Novartis, other from Gilead, personal fees and other from Rempex, outside the submitted work; P. Flume: grants and personal fees from Aptalis, grants and personal fees from Gilead Sciences, Inc, grants and personal fees from Bayer Healthcare AG, grants and personal fees from Novartis, grants and personal fees from Vertex Pharmaceuticals, Inc, grants and personal fees from Pharmaxis Limited, grants from Boehringer Ingelheim Pharmceuticals, grants from Grifols, grants from Savara Pharma, grants from KaloBios, grants from Cystic Fibrosis Foundation, grants from National Institutes of Health, grants and personal fees from Genentech, outside the submitted work; A. Munck: personal fees from Vertex, Novartis, personal fees from Vertex, outside the submitted work; F. Ratjen: personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Vertex, personal fees from Novartis, personal fees from Bayer, personal fees from Talecris, personal fees from CSL Behring, personal fees from Roche, personal fees from Gilead, grants from Novartis, personal fees from Genetech, personal fees from Genetech, personal fees from Pari, outside the submitted work; S.J. Schwarzenberg: consulting for Spark HealthCare, outside the submitted work; G. Ullrich: personal fees from Chiesi Pharma GmbH, personal fees from Novartis Pharma GmbH, personal fees from Gilead Sciences GmbH, personal fees from GSK GmbH & Co. KG, personal fees from Activaero GmbH, personal fees from Axcan Pharma GmbH, outside the submitted work. S. Bojcin, M. Bryon, A. Duff, N. Kashirskaya, I. Sermet-Gaudelus, K.W. Southern, G. Taccetti, and S. Wolfe have no conflicts of interest to report.
-  K.W. Southern, M.M.E. Mérelle, J.E. Dankert-Roelse, A. Nagelkerke. Newborn screening for cystic fibrosis. Cochrane Database Syst Rev. 2009;(1)10.1002/14651858.CD001402.pub2 [Art. No.: CD001402]
-  C. Castellani, K.W. Southern, K. Brownlee, J. Dankert Roelse, A. Duff, M. Farrell, et al. European best practice guidelines for cystic fibrosis neonatal screening. J Cyst Fibros. 2009;8:153-173 Crossref
-  I. Sermet-Gaudelus, S.J. Mayell, K.W. Southern. Guidelines on the early management of infants diagnosed with cystic fibrosis following newborn screening. J Cyst Fibros. 2010;9:323-329 Crossref
-  S.J. Mayell, A. Munck, J.V. Craig, I. Sermet, K.G. Brownlee, M.J. Schwarz, et al. A European consensus for the evaluation and management of infants with an equivocal diagnosis following newborn screening for cystic fibrosis. J Cyst Fibros. 2009;8:71-78 Crossref
-  E. Kerem, S. Conway, S. Elborn, H. Heijerman. Standards of care for patients with cystic fibrosis: a European consensus. J Cyst Fibros. 2005;4:7-26 [S1569–1993(04)00213–9 [pii]1016/j.jcf.2004.12.002.] Crossref
-  P.M. Farrell, B.J. Rosenstein, T.B. White, F.J. Accurso, C. Castellani, G.R. Cutting, et al. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr. 2008;153:S4-S14 Crossref
-  K. De Boeck, M. Wilschanski, C. Castellani, C. Taylor, H. Cuppens, J. Dodge, et al. Cystic fibrosis: terminology and diagnostic algorithms. Thorax. 2006;61:627-635 Crossref
-  ECFS CTN SOP on sweat testing. (, 2013)
-  C. Goubau, M. Wilschanski, V. Skalicka, P. Lebecque, K.W. Southern, I. Sermet, et al. Phenotypic characterisation of patients with intermediate sweat chloride values: towards validation of the European diagnostic algorithm for cystic fibrosis. Thorax. 2009;64:683-691 Crossref
-  C. Castellani, H. Cuppens, M. Macek Jr., J.J. Cassiman, E. Kerem, P. Durie, et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros. 2008;7:179-196 Crossref
-  K. De Boeck, L. Kent, J. Davies, N. Derichs, M. Amaral, S.M. Rowe, et al. CFTR biomarkers: time for promotion to surrogate end-point. Eur Respir J. 2013;41:203-216 10.1183/09031936.00057512 Crossref
-  J.A. Dodge, P.A. Lewis, M. Stanton, J. Wilsher. Cystic fibrosis mortality and survival in the UK: 1947–2003. Eur Respir J. 2007;29:522-526 Crossref
-  Cystic Fibrosis Foundation Patient Registry. 2005 Annual data report to the center directors. (Cystic Fibrosis Foundation, Bethesda, MD, 2006)
-  D.B. Sanders, R.C. Bittner, M. Rosenfeld, L.R. Hoffman, G.J. Redding, C.H. Goss. Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am J Respir Crit Care Med. 2010;182:627-632 Crossref
-  J. Emerson, M. Rosenfeld, S. McNamara, B. Ramsey, R.L. Gibson, J. Emerson, et al. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol. 2002;34:91-100 Crossref
-  S.C. Langton-Hewer, A.R. Smyth. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev. 2006;(4)10.1002/14651858.CD004197.pub3 [Art. No.: CD004197.(updated 2010)]
-  Antibiotic treatment for cystic fibrosis. Report of the UK Cystic Fibrosis Trust Antibiotic Group (UK Cystic Fibrosis Trust, London, 2009)
-  G. Ryan, M. Singh, K. D. Inhaled antibiotics for long-term therapy in cystic fibrosis. Cochrane Database Syst Rev. 2011;(3)10.1002/14651858.CD001021.pub2 [Art. No.: CD001021]
-  P.J. Mogayzel, E.T. Naureckas, K.A. Robinson, G. Mueller, D. Hadjiliadis, J.B. Hoag, et al. Cystic fibrosis pulmonary guidelines. Am J Respir Crit Care Med. 2013;187:680-689 10.1164/rccm.201207-1160OE Crossref
-  M.W. Konstan, P.A. Flume, M. Kappler, R. Chiron, M. Higgins, F. Brockhaus, et al. Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: the EAGER trial. J Cyst Fibros. 2011;10:54-61 Crossref
-  C.M. Oermann, G.Z. Retsch-Bogart, A.L. Quittner, R.L. Gibson, K.S. McCoy, A.B. Montgomery, et al. An 18-month study of the safety and efficacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis. Pediatr Pulmonol. 2010;45:1121-1134 Crossref
-  A. Schuster, C. Haliburn, G. Döring, M.H. Goldman. Group ftFS. Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study. Thorax. 2013;68:344-350 Crossref
-  Association of Chartered Physiotherapists in Cystic Fibrosis. Standards of care and good clinical practice for the physiotherapy management of cystic fibrosis. (UK Cystic Fibrosis Trust, London, 2011)
-  P.A. Flume, K.A. Robinson, B.P. O'Sullivan, J.D. Finder, R.L. Vender, D.-B. Willey-Courand, et al. Cystic fibrosis pulmonary guidelines: airway clearance therapies. Respir Care. 2009;54:522-537
-  M.P. McIlwaine, N. Alarie, G.F. Davidson, L.C. Lands, F. Ratjen, R. Milner, et al. Long-term multicentre randomised controlled study of high frequency chest wall oscillation versus positive expiratory pressure mask in cystic fibrosis. Thorax. 2013;10.1136/thoraxjnl-2012-202915
-  International physiotherapy group for cystic fibrosis. Physiotherapy for people with Cystic Fibrosis: from infant to adult (, 2009) [ http://www.cfww.org/docs/ipg-cf/bluebook/bluebooklet2009websiteversion.pdf ]
-  D.N. Homnick. Making airway clearance successful. Paediatr Respir Rev. 2007;8:40-45 Crossref
-  D.L. Wilkes, J.E. Schneiderman, T. Nguyen, L. Heale, F. Moola, F. Ratjen, et al. Exercise and physical activity in children with cystic fibrosis. Paediatr Respir Rev. 2009;10:105-109 10.1016/j.prrv.2009.04.001 Crossref
-  R. de Groot, A.L. Smith. Antibiotic pharmacokinetics in cystic fibrosis. Differences and clinical signifance. Clin Pharmacokinet. 1987;13:228-253 Crossref
-  P.A. Flume, P.J. Mogayzel, K.A. Robinson, C.H. Goss, R.L. Rosenblatt, R.J. Kuhn, et al. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009;180:802-808 10.1164/rccm.200812-1845PP Crossref
-  G. Döring, P. Flume, H. Heijerman, J.S. Elborn. Treatment of lung infection in patients with cystic fibrosis: current and future strategies. J Cyst Fibros. 2012;11:461-479
-  A.P. Jones, C.E. Wallis. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2010;(3)10.1002/14651858.CD001127.pub2 [Art. No.: CD001127.]
-  M.W. Konstan, J.S. Wagener, D.J. Pasta, S.J. Millar, J.R. Jacobs, A. Yegin, et al. Clinical use of dornase alfa is associated with a slower rate of FEV1 decline in cystic fibrosis. Pediatr Pulmonol. 2011;46:545-553 10.1002/ppul.21388 Crossref
-  E. Nash, A. Stephenson, F. Ratjen, E. Tullis. Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis. Cochrane Database Syst Rev. 2009;(1)10.1002/14651858.CD007168.pub2 [Art. No.: CD007168]
-  P. Wark, V.M. McDonald. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2009;(2)10.1002/14651858.CD001506.pub3 [Art. No.: CD001506]
-  D. Bilton, P. Robinson, P. Cooper, C.G. Gallagher, J. Kolbe, H. Fox, et al. Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study. Eur Respir J. 2011;38:1071-1080 Crossref
-  M.L. Aitken, G. Bellon, K. De Boeck, P.A. Flume, H.G. Fox, D.E. Geller, et al. Long-term inhaled dry powder mannitol in cystic fibrosis: an international randomized study. Am J Respir Crit Care Med. 2012;185:645-652 Crossref
-  K.W. Southern, P.M. Barker, A. Solis-Moya, L. Patel. Macrolide antibiotics for cystic fibrosis. Cochrane Database Syst Rev. 2012;(11)10.1002/14651858.CD002203.pub4 [Art. No.: CD002203]
-  L. Saiman, M. Anstead, N. Mayer-Hamblett, L.C. Lands, M. Kloster, J. Hocevar-Trnka, et al. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2010;303:1707-1715 Crossref
-  L.C. Lands, S. Stanojevic. Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis. Cochrane Database Syst Rev. 2007;(4)10.1002/14651858.CD001505.pub2 [Art. No.: CD001505.]
-  F.J. Accurso, S.M. Rowe, J.P. Clancy, M.P. Boyle, J.M. Dunitz, P.R. Durie, et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010;363:1991-2003 10.1056/NEJMoa0909825 Crossref
-  R. Amin, A. Dupuis, S.D. Aaron, F. Ratjen. The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis. Chest. 2010;137:171-176 Crossref
-  Standards for the clinical care of children and adults with cystic fibrosis in the UK. (UK Cystic Fibrosis Trust, London, 2011)
-  M.R. Miller, J. Hankinson, V. Brusasco, F. Burgos, R. Casaburi, A. Coates, et al. Standardisation of spirometry. Eur Respir J. 2005;26:319-338 10.1183/09031936.05.00034805 Crossref
-  V.A. Stallings, L.J. Stark, K.A. Robinson, A.P. Feranchak, H. Quinton. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc. 2008;108:832-839 [S0002-8223(08)00179-X [pii] 10.1016/j.jada.2008.02.020] Crossref
-  D. Borowitz, R.D. Baker, V. Stallings. Consensus report on nutrition for pediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nutr. 2002;35:246-259 Crossref
-  UK cystic fibrosis trust nutrition working group. (Nutritional management of cystic fibrosis, Bromley, 2002)
-  D. Stapleton, C. Ash, S. King, E V. Australasian clinical practice guidelines for nutrition in cystic fibrosis. (, 2006)
-  M. Sinaasappel, M. Stern, J. Littlewood, S. Wolfe, G. Steinkamp, H.G. Heijerman, et al. Nutrition in patients with cystic fibrosis: a European Consensus. J Cyst Fibros. 2002;1:51-75 [S1569199302000322 [pii]] Crossref
-  D. Borowitz, K.A. Robinson, M. Rosenfeld, S.D. Davis, K.A. Sabadosa, S.L. Spear, et al. Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatr. 2009;155:S73-S93 [S0022-3476(09)00881-6 [pii] 10.1016/j.jpeds.2009.09.001] Crossref
-  K.A. Robinson, I.J. Saldanha, N.A. McKoy. Management of infants with cystic fibrosis: a summary of the evidence for the cystic fibrosis foundation working group on care of infants with cystic fibrosis. J Pediatr. 2009;155:S94-S105 [S0022-3476(09)00882-8 [pii] 10.1016/j.jpeds.2009.09.002] Crossref
-  R.J. Kuczmarski, C.L. Ogden, S.S. Guo, L.M. Grummer-Strawn, K.M. Flegal, Z. Mei, et al. 2000 CDC growth charts for the United States: methods and development. Vital Health Stat. 2002;11:1-190
-  W.H.O. Multicentre Growth Reference Study Group. WHO child growth standards: methods and development: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age. (Switzerland, Geneva, 2006)
-  H. Anthony, C.E. Collins, G. Davidson, C. Mews, P. Robinson, R. Shepherd, et al. Pancreatic enzyme replacement therapy in cystic fibrosis: Australian guidelines. Pediatric Gastroenterological Society and the Dietitians Association of Australia. J Paediatr Child Health. 1999;35:125-129 Crossref
-  F.P. Edenborough, G. Borgo, C. Knoop, L. Lannefors, W.E. Mackenzie, S. Madge, et al. Guidelines for the management of pregnancy in women with cystic fibrosis. J Cyst Fibros. 2008;7(1):S2-S32 [S1569-1993(07)00129-4 [pii] 10.1016/j.jcf.2007.10.001] Crossref
-  J.R. Yankaskas, B.C. Marshall, B. Sufian, R.H. Simon, D. Rodman. Cystic fibrosis adult care: consensus conference report. Chest. 2004;125:1S-39S Crossref
-  A. Moran, C. Brunzell, R.C. Cohen, M. Katz, B.C. Marshall, G. Onady, et al. Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care. 2010;33:2697-2708 [33/12/2697 [pii] 10.2337/dc10-1768] Crossref
-  P.G. Middleton, M. Wagenaar, A.G. Matson, M.E. Craig, D.J. Holmes-Walker, T. Katz, et al. Australian standards of care for cystic fibrosis-related diabetes. Respirology. 2013;3310.1111/resp.12227 [in press]
-  American Diabetes Association. Clinical practice recommendations. Diabetes Care. 2010;33(1):S1-S100 [33/Supplement_1/S3 [pii] 10.2337/dc10-S003]
-  R.M. Aris, P.A. Merkel, L.K. Bachrach, D.S. Borowitz, M.P. Boyle, S.L. Elkin, et al. Guide to bone health and disease in cystic fibrosis. J Clin Endocrinol Metab. 2005;90:1888-1896 [jc.2004-1629 [pii] 10.1210/jc.2004-1629] Crossref
-  I. Sermet-Gaudelus, M.L. Bianchi, M. Garabedian, R.M. Aris, A. Morton, D.S. Hardin, et al. European cystic fibrosis bone mineralisation guidelines. J Cyst Fibros. 2011;10(2):S16-S23 [S1569-1993(11)60004-0 [pii] 10.1016/S1569-1993(11)60004-0] Crossref
-  U.K. Cystic Fibrosis Trust. Bone mineralisation in cystic fibrosis. (Bromley, Cystic Fibrosis Trust, 2007)
-  P.A. Flume, C. Strange, X. Ye, M. Ebeling, T. Hulsey, L.L. Clark, et al. Pneumothorax in cystic fibrosis. Chest. 2005;128:720-728 Crossref
-  P.A. Flume, P.J. Mogayzel, K.A. Robinson, R.L. Rosenblatt, L. Quittell, B.C. Marshall, et al. Cystic fibrosis pulmonary guidelines: pulmonary complications: hemoptysis and pneumothorax. Am J Respir Crit Care Med. 2010;182:298-306 10.1164/rccm.201002-0157OC
-  P.A. Flume, J.R. Yankaskas, M. Ebeling, T. Hulsey, L.L. Clark, P.A. Flume, et al. Massive hemoptysis in cystic fibrosis. Chest. 2005;128:729-738 Crossref
-  W.M. Robinson, S. Ravilly, C. Berde, M.E. Wohl. End-of-life care in cystic fibrosis. Pediatrics. 1997;100:205-209 10.1542/peds.100.2.205 Crossref
-  J.M. Clayton, K.M. Hancock, P.N. Butow, M.H. Tattersall, D.C. Currow, J. Adler, et al. Clinical practice guidelines for communicating prognosis and end-of-life issues with adults in the advanced stages of a life-limiting illness, and their caregivers. Med J Aust. 2007;186:S77-S108
-  D. Debray, D. Kelly, R. Houwen, B. Strandvik, C. Colombo. Best practice guidance for the diagnosis and management of cystic fibrosis-associated liver disease. J Cyst Fibros. 2011;10(2):S29-S36 10.1016/S1569-1993(11)60006-4 Crossref
-  R.J. Sokol, P.R. Durie. Consensus document recommendations for management of liver and biliary tract disease in cystic fibrosis. (Bethesda, Cystic Fibrosis Foundation, 1999)
-  R.J. Sokol, P.R. Durie, C.F.F.H.D.C. Group. Recommendations for management of liver and biliary tract disease in cystic fibrosis. J Pediatr Gastroenterol Nutr. 1999;28:S1-S13 Crossref
-  I. Modolell, A. Alvarez, L. Guarner, J. De Gracia, J.-R. Malagelada. Gastrointestinal, liver, and pancreatic involvement in adult patients with cystic fibrosis. Pancreas. 2001;22:395-399 Crossref
-  C.Y. Ooi, P.R. Durie. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis. J Cyst Fibros. 2012;11:355-362 10.1016/j.jcf.2012.05.001 Crossref
-  Cystic Fibrosis Foundation Patient Registry. Annual data report to the centre directors. (Cystic Fibrosis Foundation, Bethesda, 2012)
-  Y. Vandenplas, C.D. Rudolph, C. Di Lorenzo, E. Hassall, G. Liptak, L. Mazur, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49:498-547
-  R.H. Houwen, H.P. van der Doef, I. Sermet, A. Munck, B. Hauser, J. Walkowiak, et al. Defining DIOS and constipation in cystic fibrosis with a multicentre study on the incidence, characteristics, and treatment of DIOS. J Pediatr Gastroenterol Nutr. 2010;50:38-42 Crossref
-  Evaluation and treatment of constipation in children: summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2006;43:405-407
-  C. Colombo, H. Ellemunter, R. Houwen, A. Munck, C. Taylor, M. Wilschanski, et al. Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. J Cyst Fibros. 2011;10(Suppl. 2):24-28
-  A. Munck, N. Belbari, P. de Lagausie, M. Peuchmaur, J. Navarro. Ultrasonography detects appendicular mucocele in cystic fibrosis patients suffering recurrent abdominal pain. Pediatric. 2000;105:921 Crossref
-  E.M. Quigley, A. Abu-Shanab. Small intestinal bacterial overgrowth. Infect Dis Clin North Am. 2010;24:943-959 [viii-ix] Crossref
-  A. Karimi, R.R. Gorter, C. Sleeboom, C.M. Kneepkens, H.A. Heij. Issues in the management of simple and complex meconium ileus. Pediatr Surg Int. 2011;27:963-968 Crossref
-  B.E. Carlyle, D.S. Borowitz, P.L. Glick. A review of pathophysiology and management of fetuses and neonates with meconium ileus for the pediatric surgeon. J Pediatr Surg. 2012;47:772-781 Crossref
-  E.M. Gibney, D.S. Goldfarb. The association of nephrolithiasis with cystic fibrosis. Am J Kidney Dis. 2003;42:1-11 Crossref
-  H.J.C. Bonestroo, K.M. de Winter-de Groot, C.K. van der Ent, H.G.M. Arets. Upper and lower airway cultures in children with cystic fibrosis: do not neglect the upper airways. J Cyst Fibros. 2010;9:130-134 10.1016/j.jcf.2010.01.001 Crossref
-  S. Garwood, P.A. Flume, J. Ravenel. Superior vena cava syndrome related to indwelling intravenous catheters in patients with cystic fibrosis. Pediatr Pulmonol. 2006;41:683-687 Crossref
-  A. Munck, S. Malbezin, J. Bloch, M. Gerardin, M. Lebourgeois, J. Derelle, et al. Follow-up of 452 totally implantable vascular devices in cystic fibrosis patients. Eur Respir J. 2004;23:430-434 10.1183/09031936.04.00052504 Crossref
-  T.O. Hirche, C. Knoop, H. Hebestreit, et al. Practical guidelines: lung transplantation in patients with cystic fibrosis. Pulm Med. 2014;2014:621342
-  D. Sands, T. Repetto, L.J. Dupont, A. Korzeniewska-Eksterowicz, P. Catastini, S. Madge. End of life care for patients with cystic fibrosis. J Cyst Fibros. 2011;10(Suppl. 2):S37-S44 Crossref
-  E. Kerem, J. Reisman, M. Corey, G.J. Canny, H. Levison. Prediction of mortality in patients with cystic fibrosis. N Engl J Med. 1992;326:1187-1191 Crossref
-  J.B. Orens, M. Estenne, S. Arcasoy, J.V. Conte, P. Corris, J.J. Egan, et al. International guidelines for the selection of lung transplant candidates: 2006 update—a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006;25:745-755 Crossref
-  T.G. Liou, F.R. Adler, B.C. Cahill, S.C. FitzSimmons, D. Huang, J.R. Hibbs, et al. Survival effect of lung transplantation among patients with cystic fibrosis. JAMA. 2001;286:2683-2689 Crossref
-  N. Mayer-Hamblett, M. Rosenfeld, J. Emerson, C.H. Goss, M.L. Aitken, N. Mayer-Hamblett, et al. Developing cystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Am J Respir Crit Care Med. 2002;166:1550-1555 Crossref
-  G.I. Snell, K. Bennetts, J. Bartolo, B. Levvey, A. Griffiths, T. Williams, et al. Body mass index as a predictor of survival in adults with cystic fibrosis referred for lung transplantation. J Heart Lung Transplant. 1998;17:1097-1103
-  R.A. Bradbury, D. Shirkhedkar, A.R. Glanville, L.V. Campbell. Prior diabetes mellitus is associated with increased morbidity in cystic fibrosis patients undergoing bilateral lung transplantation: an ‘orphan’ area? A retrospective case–control study. Intern Med J. 2009;39:384-388 Crossref
-  M. Hofer, C. Schmid, C. Benden, R. Speich, I. Inci, W. Weder, et al. Diabetes mellitus and survival in cystic fibrosis patients after lung transplantation. J Cyst Fibros. 2012;11:131-136 Crossref
-  B.S. Quon, N. Mayer-Hamblett, M.L. Aitken, A.R. Smyth, C.H. Goss. Risk factors for chronic kidney disease in adults with cystic fibrosis. Am J Respir Crit Care Med. 2011;184:1147-1152 Crossref
-  B.S. Quon, N. Mayer-Hamblett, M.L. Aitken, C.H. Goss. Risk of post-lung transplant renal dysfunction in adults with cystic fibrosis. Chest. 2012;142:185-191
-  J. Paccou, N. Zeboulon, C. Combescure, L. Gossec, B. Cortet. The prevalence of osteoporosis, osteopenia, and fractures among adults with cystic fibrosis: a systematic literature review with meta-analysis. Calcif Tissue Int. 2010;86:1-7 Crossref
-  M.G. Slieker, J.P. van Gestel, H.G. Heijerman, G.A. Tramper-Stranders, F.T. van Berkhout, C.K. van der Ent, et al. Outcome of assisted ventilation for acute respiratory failure in cystic fibrosis. Intensive Care Med. 2006;32:754-758 Crossref
-  R.R. Bartz, R.B. Love, G.E. Leverson, L.R. Will, D.L. Welter, K.C. Meyer. Pre-transplant mechanical ventilation and outcome in patients with cystic fibrosis. J Heart Lung Transplant. 2003;22:433-438 Crossref
-  D.P. Mason, L. Thuita, E.R. Nowicki, S.C. Murthy, G.B. Pettersson, E.H. Blackstone. Should lung transplantation be performed for patients on mechanical respiratory support? The US experience. J Thorac Cardiovasc Surg. 2010;139:765-773 [e1]
-  M. Nosotti, L. Rosso, D. Tosi, A. Palleschi, P. Mendogni, I.F. Nataloni, et al. Extracorporeal membrane oxygenation with spontaneous breathing as a bridge to lung transplantation. Interact. Cardiovasc. Thorac. Surg.. 2013;16:55-59 Crossref
-  N. Sage, M. Sowden, E. Chorlton, A. Edeleanu. CBT for chronic illness and palliative care. (Wiley, Chicester, 2008)
-  W.M. Robinson. Palliative and end-of-life care in cystic fibrosis: what we know and what we need to know. Curr Opin Pulm Med. 2009;15:621-625 Crossref
-  M. Braithwaite, J. Philip, H. Tranberg, F. Finlayson, M. Gold, T. Kotsimbos, et al. End of life care in CF: patients, families and staff experiences and unmet needs. J Cyst Fibros. 2011;10:253-257 Crossref
-  K. Macdonald. Living in limbo–patients with cystic fibrosis waiting for transplant. Br J Nurs. 2006;15:566-572 Crossref
-  E. Chapman, A. Landy, A. Lyon, C. Haworth, D. Bilton. End of life care for adult cystic fibrosis patients: facilitating a good enough death. J Cyst Fibros. 2005;4:249-257 Crossref
-  I. Mitchell, E. Nakielna, E. Tullis, C. Adair. Cystic fibrosis End-stage care in Canada. Chest. 2000;118:80-84 Crossref
-  R.M. Nobili, A.J.A. Duff, G. Ullrich, U. Smrekar, T. Havermans, M. Bryon, et al. Guiding principles on how to manage relevant psychological aspects within a CF team: interdisciplinary approaches. J Cyst Fibros. 2011;10:S45-S52 10.1016/S1569-1993(11)60008-8 Crossref
-  R. Grob. Is my sick child healthy? Is my healthy child sick?: changing parental experiences of cystic fibrosis in the age of expanded newborn screening. Soc Sci Med. 2008;67:1056-1064 10.1016/j.socscimed.2008.06.003 Crossref
-  C.A. Olsson, L. Bond, J.M. Burns, D.A. Vella-Brodrick, S.M. Sawyer. Adolescent resilience: a concept analysis. J Adolesc. 2003;26:1-11 Crossref
-  A.J.A. Duff, G.J. Latchford. Motivational interviewing for adherence problems in cystic fibrosis. Pediatr Pulmonol. 2010;45:211-220 10.1002/ppul.21103
-  E. Widerman. Communicating a diagnosis of cystic fibrosis to an adult: what physicians need to know. Behav Med. 2002;28:45-52 Crossref
-  E. Widerman. The experience of receiving a diagnosis of cystic fibrosis after age 20: implications for social work. Soc Work Health Care. 2004;39:415-433
-  K. Randlesome, M. Bryon, M. Evangeli. Developing a measure of eating attitudes and behaviours in cystic fibrosis. J Cyst Fibros. 2013;12:15-21 10.1016/j.jcf.2012.05.005 Crossref
-  S.M. Sawyer. Sexual and reproductive health. M.E. Hodson, D. Geddes, A. Bush (Eds.) Cystic Fibrosis (Arnold, London, 2007) 279-290
-  M. Hogg, M. Braithwaite, M. Bailey, T. Kotsimbos, J.W. Wilson. Work disability in adults with cystic fibrosis and its relationship to quality of life. J Cyst Fibros. 2007;6:223-227 10.1016/j.jcf.2006.10.004 Crossref
-  J.L. Griffith, L. Gaby. Brief psychotherapy at the bedside: countering demoralization from medical illness. Psychosomatics. 2005;46:109-116 Crossref
-  C. Castellani, M. Macek, J.-J. Cassiman, A. Duff, J. Massie, L.P. ten Kate, et al. Benchmarks for Cystic Fibrosis carrier screening: a European consensus document. J Cyst Fibros. 2010;9:165-178 Crossref
-  C. Bombieri, M. Claustres, K. De Boeck, N. Derichs, J. Dodge, E. Girodon, et al. Recommendations for the classification of diseases as CFTR-related disorders. J Cyst Fibros. 2011;10(Suppl. 2):S86-S102 Crossref
-  G. Doring, N. Hoiby, Study G. Consensus. Early intervention and prevention of lung disease in cystic fibrosis: a European consensus. J Cyst Fibros. 2004;3:67-91 Crossref
-  H. Heijerman, E. Westerman, S. Conway, D. Touw, G. Doring. consensus working g. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus. J Cyst Fibros. 2009;8:295-315 Crossref
a Division of Child Health, Obstetrics & Gynaecology (COG), School of Medicine, University of Nottingham, UK
b Department of Thoracic Medicine, The Prince Charles Hospital, Australia
c Queensland Children's Medical Research Institute, Brisbane, Australia
d Cystic Fibrosis Europe, Denmark
e Cystic Fibrosis Unit, Great Ormond Street Hospital for Children, London, UK
f Regional Paediatric CF Unit, The Leeds Children's Hospital, Belmont Grove, Leeds LS2 9NS, UK
g Medical University of South Carolina, Charleston, SC, USA
h Department of Cystic Fibrosis, Research Centre for Medical Genetics, RAMS, Moscow, Russia
i Assistance publique-Hôpitaux de Paris, Hôpital Robert Debré, Paediatric Gastroenterology and Respiratory Department, CF Centre, Université Paris 7, 75019, Paris, France
j Association française pour le dépistage et la prévention des handicaps de l'enfant (AFDPHE), France
k Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Canada
l Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, University of Toronto, Canada
m Pediatric Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Amplatz Children's Hospital, Minneapolis, MN, USA
n INSERM U1151, France
o Université René Descartes Paris 5, France
p Unité fonctionnelle de Mucoviscidose, Service de Pneumo-Pédiatrie, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743, Paris, France
q Department of Women's and Children's Health, University of Liverpool, UK
r Institute of Child Health, Alder Hey Children's Hospital, Eaton Road, Liverpool L12 2AP, UK
s Cystic Fibrosis Centre, Department of Paediatric Medicine, Anna Meyer Children's University Hospital, Florence, Italy
t Reutzstr. 1, 19055, Schwerin, Germany
u Paediatric Cystic Fibrosis, Regional Paediatric CF Unit, The Leeds Children's Hospital, Belmont Grove, Leeds LS2 9NS, UK
v Macedonian Cystic Fibrosis Association, Misko Mihajlovski 15, 1000 Skopje, Republic of Macedonia
Definition; an infant with a repeatedly intermediate sweat test result, or an infant with two CFTR gene mutations (one of which has unclear phenotypic outcome) and a normal or intermediate sweat test result. An intermediate sweat test result is a sweat chloride value between 30 and 59 mmol/L  .
© 2014 European Cystic Fibrosis Society., Published by Elsevier B.V.
European Cystic Fibrosis Society Standards of Care: Framework for the Cystic Fibrosis CentreMon, 08/18/2014 - 18:59
A significant increase in life expectancy in successive birth cohorts of people with cystic fibrosis (CF) is a result of more effective treatment for the disease. It is also now widely recognized that outcomes for patients cared for in specialist CF Centres are better than for those who are not. Key to the effectiveness of the specialist CF Centre is the multidisciplinary team (MDT), which should include consultants, clinical nurse specialist, microbiologist, physiotherapist, dietitian, pharmacist, clinical psychologist, social worker, clinical geneticist and allied healthcare professionals, all of whom should be experienced in CF care. Members of the MDT are also expected to keep up to date with developments in CF through continued professional development, attendance at conferences, auditing and involvement in research. Specialists CF Centres should also network with other Centres both nationally and internationally, and feed Centre data to registries in order to further the understanding of the disease. This paper provides a framework for the specialist CF Centre, including the organisation of the Centre and the individual roles of MDT members, as well as highlighting the value of CF organisations and disease registries.
Keywords: CF Centre, Multidisciplinary team, Continuing professional development.
People with cystic fibrosis (CF) have complex care needs that demand specialist, medical and allied healthcare expertise. The life expectancy has increased significantly in successive patient birth cohorts  as a result of more effective treatments and crucially because most patients attend CF Centres in line with the demonstration that patients who attend CF Centres for their care have better well-being and lung function than those who do not  and . Thus, the CF Centre has become the model of care for people with CF; patients should receive full care from the Centre or have local directed care supervised by the Centre , , and .
The framework of the CF Centre is formed by a multidisciplinary team (MDT), links with other medical and surgical specialties, the buildings and facilities, and the hardware and software that combined allow the MDT to provide a level of care that meets the complex medical challenges of this disease using effective diagnostics and holistic treatment programmes.
The MDT members are at the core of the CF Centre and should be supported with continuing professional development (CPD), audit and research. Each discipline should establish its own rigorous framework, to ensure that patients' needs related to their discipline are met. The CF Centre should have adequate resources (e.g. staffing, IT equipment) and an infrastructure (inpatient and outpatient facilities) that allow the MDT to provide a level of care that is in accordance with the European Cystic Fibrosis Society (ECFS) standards recommended in this document, ensuring a safe, cost-effective and high-quality service. It is recognized that this may not be immediately achievable throughout Europe, particularly in countries with a low gross domestic product. It is crucial that where these standards cannot be met, procedures are put in place to enable them to do so within the short- to mid-term future, and that the hospital management commits to supporting CF clinicians. Without proper resources, a Centre is at risk of providing uncoordinated and substandard care. A lack of homogeneity in CF care will impact on patient outcomes  .
At present, access to specialist CF services across Europe is inconsistent. Qualifications, training and roles vary considerably. Clinical practice should where possible be evidence based and reflect current research findings, clinical guidelines and consensus views. CF specialist professionals should be appropriately trained, qualified and registered by the state/national health authorities and legally recognized to practice within that country. Specialists should practice within their professional code of conduct and competency. They have a responsibility to maintain, update and enhance their knowledge, skills, efficacy and expertise through a proactive approach to continuing professional development. Participation in uni- and multi-professional audit and research, benchmarking, external quality assessment schemes, service evaluation, development and improvement, both of the specialist service and its provision as a whole is essential. As a CF Centre may be the only facility in a city or region, national and international programmes to support CPD, benchmarking and service improvement are strongly encouraged.
The following sections describe the ECFS recommended standards for the individual specialties within the CF Centre.
2. Framework for the paediatric and adult Centres
Paediatric and adult CF Centres have many features in common, so that the requirements outlined below usually apply to both. As the health of children and adolescents continues to improve, the emphasis in paediatric care is on the prevention of disease progression. The morbidity and almost all of the mortality associated with CF have shifted to adults. Adult services should take into account the greater demands for inpatient provision and the higher prevalence of multisystem complications. Even before the transition from paediatric to adult care, it is most important that the two Centres work closely together. Regular meetings between the teams and shared protocols can smooth the transition process for the young adult and minimize the changes to their treatment. Effective communication between teams during this period is crucial to the success of the transition process.
Children with CF will have their care transferred to adult services around the time of their 17th/19th birthday. Children, and their families, should understand that they will transfer to an adult Centre at this age. The paediatrician is not trained or experienced to manage the emotional, social, or medical demands of the adult patient. In the adult population, the manifestations of this multisystem disease (e.g. CF-related diabetes, osteoporosis, renal and liver complications and atypical infection) are significantly more problematic. The adult physicians are also best placed to fully inform patients about the potential risks of pregnancy and are competent in the non-obstetric care of pregnant women with CF.
The young person with CF and his/her family must be involved in planning transfer at an early stage. The topic should be introduced when the diagnosis of CF is made and reinforced at appropriate intervals thereafter. Practical discussions should start at around 11 years of age in the context of educational, social and sexual conversations about growing up with a long-term condition. There must be close liaison with an agreed protocol for transition, and coordinators from both teams should be identified. The adolescent and his/her carers should have the opportunity to formally meet the adult team on more than one occasion. This is optimally achieved by having joint clinics with the adult team during the transition process. An opportunity to visit the adult facilities should be made available to patients and parents. Written information about each patient must be given to the adult team at the time of handover.
2.1. The Centre
Many of the required features are the same for adult and paediatric Centres. The CF Centre should have appropriate staff and facilities to provide comprehensive care and be capable of treating all CF-associated complications  . Patients should have direct access to the Centre 24 h a day.
In order to justify and maintain an appropriate level of expertise and experience, a specialist Centre should have a minimum of 100 adults or children with CF. In some circumstances, the geographical location of a specialist CF Centre, or a low disease frequency in certain populations, may mean that the number of patients seen by a Centre is less, but never below 50. Centres with fewer than 100 patients should be linked to a larger Centre until there are sufficient patients, experience and resources to run an independent service.
All patients with CF must have access to the Centre for routine and emergency care and advice. Patients should be reviewed regularly at a frequency appropriate to their individual needs. Routine appointments for people with stable disease should be every 2–3 months depending on the severity of their disease. Newly diagnosed infants should be seen more frequently (initially weekly).
All patients should have an annual assessment to ensure that, as a minimum, a full medical, dietetic, physiotherapy and psychosocial review is performed once a year and that all surveillance blood tests are requested. The report should be written by a consultant who should discuss the review findings with the patient/carers, and the treatment plan should be agreed by all.
2.2. The multidisciplinary team
A core MDT of trained and experienced CF specialist healthcare professionals should be responsible for patient care. The MDT should be of appropriate size for the clinic population and should include the following CF specialists and support staff:
- respiratory paediatrician/pulmonologist
- clinical microbiologist
- medical support from trainee(s)
- clinical nurse specialist
- specialist physiotherapist
- specialist dietitian
- clinical psychologist
- social worker
- clinical geneticist
- secretarial support
- database coordinator.
There should be clear medical leadership of the MDT. The roles and responsibilities of all senior doctors in the team should be clearly defined.
The ECFS concurs with the staff numbers for paediatric and adult Centres recommended by the UK CF Trust (Table 1 and Table 2)  . These numbers may vary according to health care organisation, geographical factors and local/regional variations in CF services. For example, the numbers of physiotherapists may vary according to the proportion of patients who self-administer intravenous antibiotics at home. Staffing numbers should reflect the model of shared care being used, taking into account time spent by staff from the specialist Centre in assessing and treating patients in a local hospital CF clinic. In addition, it is important that adequate cover is available for annual leave, study leave, and untoward events.
The MDT 50 patients 150 patients ≥ 250 patients b Consultant 1 0.5 1 1 Consultant 2 0.3 0.5 1 Consultant 3 – – 0.5 Medical trainees 0.8 1.5 2 Specialist nurse 2 3 4 Physiotherapist 2 3 4 Dietitian 0.5 1 1.5 Clinical psychologist 0.5 1 1.5 Social worker 0.5 1 1 Pharmacist 0.5 1 1 Secretary 0.5 1 2 Database coordinator 0.4 0.8 1
a Patients with CFTR-related disorders should not be counted.
b When clinics care for significantly more than 250 patients, additional consultants should be added to the multidisciplinary team (MDT) at a rate of approximately one additional consultant per extra 100 patients. Additional allied health professionals and support staff will also be required. There is likely to be a limit to the number of patients who can be cared for effectively in a CF Centre. This number will vary according to the facilities available in the hospital housing the Centre and the capacity of that hospital to support adequate staffing for the Centre. The MDT in individual Centres should review patient numbers annually and appreciate when resources are becoming stretched beyond the limit allowing care to be delivered to the standards recommended in guidelines. Paediatric patient numbers are likely to remain relatively stable but adult numbers are increasing every year. The need to establish a new adult Centre in any region must be considered proactively. Supply must precede, or coincide with, need.
The MDT 100 patients 150 patients ≥ 250 patients b Consultant 1 0.5 1 1 Consultant 2 0.3 0.5 1 Consultant 3 – – 0.5 Staff grade/fellow 0.5 1 1 Specialist registrar 0.4 0.8 1 Specialist nurse 2 3 5 Physiotherapist 2 4 6 Dietitian 0.5 1 2 Clinical psychologist 0.5 1 2 Social worker 0.5 1 2 Pharmacist 0.5 1 1 Secretary 0.5 1 2 Database coordinator 0.4 0.8 1
a Patients with CFTR-related disorders should not be counted.
b See footnote in Table 1 .
All members of the MDT must be registered with their relevant national health profession's council/body, and be a member of their national or international CF special interest group. They must have specialist knowledge and be experienced in the care of children and/or adults with CF. They must maintain CPD through attendance at local study days and national and international CF conferences.
2.3. Access to other specialists
It is essential that there is access to other medical and surgical specialists as needed. Essential supporting disciplines and services include: gastroenterology and hepatology (with expertise to perform emergency endoscopic ligation of oesophageal varices); diabetes and endocrinology; ear, nose and throat surgery; cardiothoracic and general surgery; specialist anaesthesia and pain control; rheumatology; nephrology; obstetrics and gynaecology; psychiatry; intensive care; and interventional radiology (with expertise to perform emergency bronchial arterial embolization, and elective percutaneous ultrasound-directed gastrostomy).
2.4. Centre infrastructure
The facilities at the CF Centre must be appropriate for all age groups. There should be sufficient capacity within the Centre for outpatients to be seen urgently whether this is within a clinic session, in a day-case unit or during a ward visit. The number of inpatient beds should be sufficient to allow non-urgent patients to be admitted within 7 days and urgent patients to be admitted within 24 h. The hospital ward nursing staff who are in contact with patients should have sufficient knowledge and experience of CF care. Finally, there should be resources and staffing available for home intravenous antibiotic administration supervised by trained outreach nurses.
All CF Centres must have a clear policy for infection prevention and control, and facilities must allow for adequate patient segregation to prevent cross-infection. Patients should not share rooms, bathrooms or toilets during a hospital stay and should not be in contact with each other in waiting areas, such as in CF clinics, wards, the pharmacy and radiology departments.
2.6. Access to specialist investigations
Within the specialists CF Centre, there should be easy access to specialist investigations. These include biochemistry and haematology laboratories for routine tests as well as analysis of sweat and measurement of fat-soluble vitamin levels, aminoglycoside levels, and measures of glucose metabolism (including continuous glucose monitoring systems). The microbiology services should have the ability to process samples from people with CF and to reliably detect Burkholderia spp., non-tuberculous mycobacteria, and fungal infection. Molecular pathogen typing and immunology for allergic bronchopulmonary aspergillosis monitoring should also be available.
Physiology must include lung function measures (both ward and outpatient spirometry), pulse oximetry including overnight O2/CO2 monitoring, exercise testing and fitness-to-fly testing.
The radiology and nuclear medicine service should include computed tomography (CT) scanning, liver ultrasound, and dual energy X-ray absorptiometry (DXA scan) bone scanning. High-frequency pure tone audiometry and flexible bronchoscopy should also be available.
Facilities must exist for a parent/carer to stay with their child in hospital, and for a child to receive suitable education within the hospital if they cannot attend school due to illness. Related to these facilities should be access to appropriate play and/or recreation, with facilities for study.
The CF Centre should be committed to active participation in clinical and translational research, and encourage patient participation in clinical trials. Each Centre should aim to be part of the expanding European Clinical Trials Network ( www.ecfs.eu/ctn ).
2.8. European policy aspects of CF Centre care
CF is a rare disease (i.e. < 1 in 2000), and as such belongs to the domain of several European Union (EU) policy initiatives relevant to research and healthcare. CF Centres, in compliance with the European Committee of Rare Disease Experts guidelines for Centres of Expertise for rare diseases, could operate within the frame of the newly established European Reference networks for rare diseases. As a rare disease, CF has a special status (Art. 54) in the Cross-Border Directive that facilitates exchange of expertise and eventually patients, and could thus address disparities in care. The development of CF Centre care in EU member states is supported by the EU Council Recommendation on action in the field of rare diseases (EC 2009/C 151/02). The introduction of orphan medical products into CF care also falls into such policy initiatives.
3. Framework for the specialist doctor
3.1. The CF consultant
The Consultant who works in a specialist CF Centre should have received accredited training in paediatric or adult CF care, usually within the context of respiratory specialization. The knowledge and skills that the CF Consultant should have acquired are detailed below  .
The CF Consultant should have knowledge of the epidemiology and pathophysiology of CF and the aetiology of respiratory and non-respiratory manifestations and complications of CF, including massive haemoptysis, pneumothorax, respiratory failure, gastrointestinal disease, diabetes, problems of fertility and pregnancy (adult care) and psychosocial problems. The relevant investigations required, including microbiological investigations, non-invasive imaging modalities such as chest X-ray, CT imaging scans, should be familiar to the Consultant. The CF Consultant also needs to be familiar with the pharmacology of inhaled, oral and systemic drugs that are prescribed to patients and with the varied interventions employed by physiotherapists. The nutritional requirements of individual patients should be monitored and enteral tube feeding initiated when appropriate.
Finally, the CF Consultant should know the indications for lung transplantation and be experienced in discussing this option with patients and carers.
CF Consultants should be able to apply the above knowledge to the management of respiratory and non-respiratory manifestations and complications. They should also be able to interpret the results from sputum microbiology tests and evaluate the functional status of patients. CF Consultants should also have good communication skills so that they can educate their patients and carers as the disease evolves.
The CF Consultant's job plan should include adequate time allocation for CF patients, both for clinical tasks as well as managerial duties. This must include the capacity to maintain his/her own CPD in CF, which should involve attendance at national or international respiratory/CF meetings. In order to keep up to date with advances in treatment and research, the CF Consultant should spend a minimum of 50% of his/her working time dedicated to CF issues.
3.2. The clinical lead
The Director of the specialist CF Centre is usually the Clinical Lead and will be expected to lead the CF MDT. He/she should act as a link between clinical experts and the hospital management. The Clinical Lead/Centre Director will be expected to head the team and to ensure that: the needs of its members are met in terms of professional development and adequate support; that opportunities for attendance at national and international CF meetings are available; and that research is encouraged. The Director should also ensure that a team approach is maintained and that all members of the CF MDT have the opportunity to have their observations and opinions considered in patient management.
It is essential that the Director understands the financial framework underpinning the country's healthcare system in order to develop and protect the financial support needed for the CF service. The Director should lead on staff recruitment, aiming to realize the human resource numbers as recommended in these Standards of Care. He/she should ensure that CF MDT meetings are held weekly, that Centre outcome measures are audited and that the results are reported back to the team so that standards of care are improved. In order to achieve the latter, the Director needs to oversee accurate data collection and documentation and that transfer of these data to the national and European registries is carried out.
In some Centres there may be co-leads/directors of the service. Clear definition of responsibility and communication is essential in this situation.
4. Framework for specialist nursing care
4.1. The role of the CF Clinical Nurse Specialist
The role of the CF Clinical Nurse Specialist should include  :
- education, advocacy and psychosocial support, particularly at important times such as:
- ○ notification of a screening result and diagnosis
- ○ first admission to hospital
- ○ first course of intravenous antibiotics
- ○ a second diagnosis (e.g. CF-related diabetes)
- ○ transition from paediatric to adult care
- ○ reproductive issues, pre- and postnatal care
- ○ transplant and end-of-life issues
- provision of support and education at home, particularly for home intravenous antibiotic therapy, nebulizer therapy, enteral feeding and non-invasive ventilation
- provision of education to others about CF, including nurseries, schools, places of higher education and work places
- acting as a link between the patient and family, primary care, community services and hospital
- acting as a resource for training and education of other professionals involved in CF care.
4.2. Access, availability and facilities
There should be an adequate number of Clinical Nurse Specialists with expert knowledge of CF in the MDT  . The CF Clinical Nurse Specialist should deliver skilled support, advice and care directly to the patient and family wherever it is needed, both when attending hospital and at home. The service will vary according to differing patient populations, their needs and requirements. The role of the CF Clinical Nurse Specialist should continuously develop to meet the needs of the local CF population  .
CF Clinical Nurse Specialists need sufficient time, office space, computer/printer and financial support in order to be able to provide a reliable service. They should stay in regular contact with patients and families in between clinic visits and therefore need access to technology such as email, phone and SMS texting.
4.3. Key stages for delivery of care
Diagnosis through newborn screening is now common in many countries. The CF Clinical Nurse Specialist plays an active role in talking to parents at diagnosis and providing ongoing support and continuing education following the initial discussion. Where screening is not available, the CF Clinical Nurse Specialist plays a similar role offering support, advice and education, which has to be individualized at a level and frequency to meet differing needs, whether diagnosis is within the first year of life, in older children or during adulthood. Contact between the CF Clinical Nurse Specialist and the patient/parent is therefore essential, whether this is in hospital, through home visiting, or via email or telephone.
For many, after coming to terms with the diagnosis and learning how to carry out treatment regimens while adjusting back to family life, the early years can seem almost normal. However, there are a few areas where the CF Clinical Nurse Specialist can provide education, practical advice and psychosocial support  , such as: administering medication; nutrition; adjusting pancreatic enzyme replacement therapy (judging the correct amount or offering advice when the child refuses to take the enzymes) in conjunction with the CF Dietitian; recognizing chest infections and making decisions about when to ask for advice or to start treatment; managing airway clearance and exercise in conjunction with the CF Physiotherapist; starting nursery; dealing with siblings; planning further children.
4.3.3. School age
When a child starts school it can be a traumatic experience for any parent. When the child has CF, parental anxiety about loss of control is likely. Many CF Clinical Nurse Specialists will visit the school (with parental permission) to educate and prepare teachers for managing CF in areas such as: maintaining good nutrition at school; administration of pancreatic enzymes and other medication (e.g. nebulizers/inhalers/oral); liaising with the school nurse; facilitating time off for hospital visits/admissions; dealing with the child's growing independence; advising on issues surrounding non-adherence, especially eating and airway clearance. The CF Clinical Nurse Specialist can help parents at this time, particularly with outreach contact as it gives parents time away from the clinical setting and allows them to discuss their anxieties in a safe and familiar environment.
Most school-age children with CF are relatively well and take part in all academic, sporting and social activities provided by the school. Occasionally, extra treatment is necessary. Supporting treatments such as intravenous therapy or enteral feeding in the home often allows children to continue attending school. The provision of an outreach service can help, as routine checks (such as spirometry) can be performed by the CF Clinical Nurse Specialist, and problems can be identified early  and .
Adolescents with CF go through the same physical and emotional changes and have the same expectations as their healthy peers, irrespective of the severity of lung disease  . The CF Clinical Nurse Specialist should be able to have open and honest discussions about issues such as: recreational drug use and the effects on CF; sexuality, safe sex and contraception; fertility and pregnancy; further education and employment; body image and self-esteem; adherence to treatment regimens; relationships with parents; promotion of self-care, adherence and responsibility; accurate information about their disease and treatment.
CF Clinical Nurse Specialists need to be sensitive and honest when giving information to young people with CF , , and . Much of the information they (and their families) receive is from peers, the media and the Internet. Information given by the CF Clinical Nurse Specialist must therefore be correct and up to date.
4.3.5. Transition from paediatric to adult care
All children with CF should move from paediatric to adult care. The importance of getting this transition process right is widely recognized  and . Transition from paediatric to adult care happens at a time when the young person with CF is moving into adulthood in other areas of their life, such as further education or employment, forming relationships and taking more responsibility for their own lifestyle. Transition can therefore be difficult for many reasons. CF Clinical Nurse Specialists involved with the transition process need to be aware of the many barriers that can prevent this process being successful  and . Both the paediatric and adult CF Clinical Nurse Specialists play an important role in ensuring a successful transition and will manage details such as: patient and parent involvement in decision making; clear communication between paediatric and adult CF MDTs; appropriate transition clinics involving the MDT; ensuring attendance at the adult clinic with appropriate follow-up.
Young people may find that their first admission to the adult Centre is to an unfamiliar ward where they do not know the staff. For these individuals and their families, the first inpatient admission requires an increase in awareness and sensitivity from the ward staff and further CF Clinical Nurse Specialist support to both the patient and the family. The CF Clinical Nurse Specialist should liaise between the ward and the CF MDT.
4.4. Adult issues
CF Clinical Nurse Specialists play a vital role in helping adults maintain a balance between adhering to treatment and their lifestyle, and recognize the need to help individuals adapt treatment regimens to suit them. This will include: educating employers and work colleagues; liaison with government agencies and the work place to ensure maximum support (financial and practical) to enable patients to stay employed or to re-train; advocacy on a patient's behalf with local social services; educating and liaising with family doctors and local pharmacists; negotiating easier access to classes at school or university; increasingly, CF Clinical Nurse Specialists will work in collaboration with the family doctor, social services and the CF team to support patients caring for their ageing parents; providing education, counselling and support around reproductive issues for both men and women with CF; practical and emotional support throughout the neonatal and postnatal periods.
Complications occur more commonly in older patients with CF , , and . An outreach service led by a CF Clinical Nurse Specialist may have to manage complex medication regimens and organise care to help maintain a lifestyle/treatment balance.
4.5. Transplantation and end-of-life issues
When admissions become more frequent, longer in duration and the burden of treatment increases, patients or their families may wish to raise the issue of lung transplantation. Early discussion with the team raises questions and concerns for both patients and their families. The CF Clinical Nurse Specialist's role as advocate and educator for the patient is vital in this decision process.
CF continues to be life limiting. Death in childhood, although uncommon, does occur. Unlike other chronic diseases, the end stages of CF can be difficult to recognize. Patients often need opportunities to discuss their fears and anxieties but may feel uncomfortable or protective talking about these issues with their family for fear of upsetting them or ‘letting them down’. Advocacy allows the CF Clinical Nurse Specialist to facilitate discussion between the patient and family. Early discussion about an individual's wishes for the terminal stage of their disease is essential to aid appropriate care planning. Issues that may be raised include transplantation, wills, funeral arrangements, writing letters or diaries to the family and where they would like to be when they die  and .
The CF Clinical Nurse Specialist plays a key role in providing individual emotional support for parents/partners. Although some families are willing to return to the hospital, many find this difficult. Visiting the family at home allows bereavement support to be offered in a safe and comfortable environment. Home visiting also allows other family members, siblings or grandparents for example, to receive support.
4.6. Core competencies, qualifications and professional development
4.6.1. Core competencies
The CF Clinical Nurse Specialist should be competent in the following key areas.
- Clinical practice
- Diagnostic and assessment skills
- Treatment skills
- Recognizing and monitoring change
- Facilitating programmes of care
- Clinical research and audit
- Knowledge of CF and associated issues
- Evidence-based practice
- Teaching and training: patients, carers, other healthcare professionals
- Patients and carers
- Liaison with clinical, social, educational, employment and other lay agencies
- Support and advocacy
- Social care
- Counselling skills
- Legal and ethical issues.
4.6.2. Qualifications and professional development
The CF Clinical Nurse Specialists must be registered as licensed practitioners in their country. They should also have specialist knowledge and be experienced in the care of children (including specific paediatric training) and/or adults with CF. The CF Clinical Nurse Specialist must contribute to research in all areas of CF, either through developing individual projects or participating in research carried out by the CF MDT, and maintain CPD through attendance at courses and conferences.
CF is a demanding disease to manage for the patient, family and the CF MDT. The CF Clinical Nurse Specialist must act as a link between the patient and family, primary and community services, and the hospital. The CF Clinical Nurse Specialist has a responsibility to ensure that every patient receives appropriate care for their individual needs. Patients should receive lifelong support and good-quality treatment through the coordination of care between patient and family, community services and hospital, both practically and through support and advice.
5. Framework for physiotherapy care
The specialist CF Physiotherapist should take the lead in providing high-quality treatment of airway clearance, physical exercise and inhalation therapy. Physiotherapy programmes in CF care are primarily preventive, and regular input is required from the time of diagnosis. The aims of therapy are to maintain ventilation in all parts of the lungs, to postpone progression of pulmonary disease, to stimulate establishment and retention of normal physical capacity and to avoid pain and musculoskeletal complications due to pulmonary or bone disease  . The CF Physiotherapist should also develop strategies for the management of complications or co-morbidities experienced by the ageing patient and should optimize the respiratory physiotherapy programme, which includes highly technical equipment, non-invasive ventilation and physical exercise with oxygen supplementation. Physical rehabilitation is essential for patients on a transplant waiting list.
5.1. The role of the CF physiotherapist
The CF Physiotherapist should be available for regular contact and assessment of the patient for treatment, lung function testing, physical surveillance and therapy evaluation. The frequency of this will vary according to the patient's age and clinical status but as a minimum should happen at every routine outpatient clinic and daily during each hospitalization (including when patients are admitted under the care of other specialists and to intensive care). A more extensive assessment should take place annually.
5.2. Regular assessment and therapy
Regular lung assessments by the CF Physiotherapist should include lung function test data, respiratory signs, degree of dyspnoea, oxygenation cough characteristics and questioning about activity of everyday life. All interventions should be tailored to the individual, with consideration of their age, severity of disease, physical side-effects or complications, and social and domestic circumstances.
5.2.1. Inhalation therapy
As the CF Physiotherapists are responsible for inhalation therapy they should be familiar with techniques, equipment provision and appropriate maintenance of devices. There is a need for consideration of timing of inhalations in relation to airway clearance as there may be a positive interdependence between the two. Education of patients in appropriate inhalation techniques is essential for optimal deposition of inhaled drugs. The CF Physiotherapist should be familiar with the appropriate nebulizer systems proven to be safe and effective in the delivery of the medications prescribed. Cleaning and maintenance of the whole nebulizer system are essential to ensure that medications are delivered optimally and safely  and .
5.2.2. Airway clearance therapy
Physiotherapists are responsible for airway clearance therapy. This involves knowledge and experience of the full range of techniques available and immediate evaluation of therapy, for example by expiratory sounds, sputum volume and characteristics and by ability to control cough. Alternative physiotherapy techniques should be recognized and considered for individual patients. There are a variety of effective airway clearance techniques that allow patient independence. These are based on sound physiological concepts and allow the CF Physiotherapist to individualize treatment programmes  . There is no standard airway clearance regimen or conclusive evidence to promote one technique over another , , , , , , , , , , and .
5.2.3. Postural and musculoskeletal assessment
Assessment of postural and musculoskeletal function is carried out to evaluate therapy. Physical exercises aimed at the maintenance of good posture and chest mobility should be included in the treatment from the beginning. As with all physiotherapy interventions the exercises should be individually tailored to each patient , , and .
5.2.4. Exercise capacity
Exercise capacity and the opportunities for exercise prescription for the person with CF include any pre-transplantation preparation. Reduction in exercise capacity is associated with a decline in respiratory function and survival  and . Physical exercise has been reported to improve lung function and decrease habitual inactivity in children with CF  . The CF Physiotherapist should perform regular exercise testing with a frequency dictated by disease progression, and in cases of specific needs like transplantation assessment or evaluation of a treatment. Care should be taken when prescribing exercise activities for patients with advanced disease, particularly when they may also experience haemoptysis, exercise-induced desaturation requiring supplementary oxygenation, pulmonary hypertension, cor pulmonale, joint arthropathies and other co-morbidities  . The CF Physiotherapist should also assess supplementary oxygen needs, for exercise or ambulation  and .
5.2.5. Non-invasive ventilation
It is recognized that non-invasive ventilation is a useful therapeutic adjunct to support airway clearance therapy and reduce the work of breathing and fatigue experienced by the severely ill patients during treatment. Non-invasive ventilation may also be useful during exercise management to decrease breathlessness, improve oxygenation and, consequently, to maintain or improve exercise tolerance , , and . Additionally, non-invasive ventilation is implemented to facilitate optimal function in patients with end-stage disease and possibly as a bridge to transplantation  .
5.2.6. Other considerations and assessments
Surveillance regarding the incidence of urinary and faecal incontinence should also be the responsibility of the CF Physiotherapist. A sensitive and open approach with early recognition of symptoms should be adopted; questioning can occur as early as 10 years of age  and .
The CF Physiotherapist should also be responsible for:
- management of associated complications and issues with adherence while continuing to promote independence that is age appropriate
- appropriate inhalation and airway clearance therapy and physical exercise programmes during pregnancy 
- ensuring the appropriate maintenance and function of equipment provided for therapy and nebulization
- the education of patients, carers, teachers and local physiotherapists; the physiotherapists should work closely with the other professionals for the benefit of the patients' holistic care
- palliative care, especially in relation to relieving dyspnoea in the terminally ill, and advising on when to withdraw non-invasive ventilation.
5.3. Service provision
When patients are resident in hospital for the treatment of an exacerbation or for routine management they should be reviewed by the CF Physiotherapist within 24 h of admission, and a treatment plan focusing on airway clearance, inhalation therapy and exercise tolerance should be implemented. The CF Physiotherapist should have a comprehensive knowledge of all techniques, respiratory pathophysiology, the rationale for alternative approaches and any associated contraindications to the treatment techniques available  . CF physiotherapy services should be available 7 days a week, with an out-of-hours physiotherapy service available for those patients who may deteriorate overnight.
5.4. Professional development, research and availability
Education, clinical audit, research and contribution to a CF registry should be pursued. CPD is integral to the work of the CF Physiotherapist who should maintain and increase specialist knowledge by attendance at relevant postgraduate courses, lectures, and national and international conferences. They should preferably be an active member of their national CF physiotherapy group and be available to represent physiotherapy interests for their country at meetings of the International Physiotherapy Group for CF (IPG/CF)  . The CF Physiotherapist should contribute to research, development and evaluation by performing audits, participating in multicentre studies and contributing data to registries. They should collect annual data in order to evaluate their care  and .
6. Framework for dietetic care
A normal nutritional status is positively associated with better lung function  and . Healthy body weight, height and BMI are positively associated with survival , , and . Ensuring normal growth in children and adolescents and maintaining a normal BMI in adults is essential.
Specialist CF Dietitians have an integral role to play in patient management and have overall responsibility for the delivery of expert nutritional care. They should be actively involved in the nutritional training, education, development and support of other healthcare professionals involved in CF care. Dietetic intervention should be both proactive and reactive, evolving in response to the needs of each individual patient. It is essential that the specialist CF Dietitian has expertise in managing the complex nutritional challenges and rare complications of the disease.
6.1. The role of the specialist CF dietitian
The specialist CF Dietitian should take the lead in providing high-quality treatment and care to ensure optimal nutritional status, including nutritional screening and surveillance, and regular patient assessment with review of all aspects of nutrition and gastrointestinal status. The frequency and type of assessment will vary with age and clinical status.
The specialist CF Dietitian should advise and educate patients and carers about the principles of nutritional management in CF to enable them to meet their nutritional needs and achieve optimal growth, weight and body composition. Advice may be required on the management of pancreatic insufficiency, fat-soluble vitamin deficiency, altered gastric motility, gastro-oesophageal reflux, impaired glucose tolerance/diabetes, reduced bone mineral density, renal disease and liver disease.
Age-specific individualized advice should be offered. This advice should consider psychosocial barriers (especially during adolescence) and be supported by written literature, visual, audio and/or audiovisual aids, computerized learning packages and ‘apps’. This is an ongoing and evolving process and must take into account the key times that may require more intensive dietetic intervention and support, such as diagnosis, early infancy, initiation of pancreatic enzyme replacement therapy, weaning, adolescence and self-management, pregnancy, initiation of enteral tube feeding, diagnosis of CF-related diabetes, transplantation and end-of-life care.
It is important to remember that patients diagnosed later in life tend to present atypically and have unique educational requirements. Improving adherence to the many prescribed nutritional therapies is a key challenge. The specialist CF Dietitian should provide a collaborative approach to increase motivation to change and support patients' efforts to change. This is based on providing information and facilitating open discussion. It is important to address emotional and perceptual barriers to adherence, e.g. a reluctance for females to gain weight during adolescence.
6.2. Clinical governance, research and quality framework
The specialist CF Dietitian should be a member of, and an active participant in, specialist interest groups locally, nationally and internationally, (e.g. European Cystic Fibrosis Nutrition Group) in order to support their practice. They should be encouraged to be an Allied Healthcare Professional Member of the European Cystic Fibrosis Society.
6.3. Dietary assessment
6.3.1. The annual assessment
Dietetic staffing should allow for a structured annual assessment of dietary intake and nutrition. Formal assessment of dietary intake using a written diet and enzyme diary should be targeted at selected individuals only; in large CF Centres, such an exercise is unsustainable if applied to all patients and is unlikely to provide additional information for patients with stable nutritional status. The annual evaluation should address all aspects of nutritional status assessment, nutritional intake, pancreatic enzyme replacement therapy, and the management of nutritional and metabolic complications. The annual assessment will help to provide the framework for future care planning and anticipatory guidance.
The reader is referred to the document “European Cystic Fibrosis Society Standards of Care: Best Practice guidelines – Optimal Nutrition and Management of Metabolic Complications of Cystic Fibrosis” for details on the assessment of the following:
- pancreatic status and absorption
- growth and nutritional status
- bone mineral density, and
- glycaemic status.
6.4. Service provision framework
Traditionally the framework for service provision is divided into:
- inpatient care
- outpatient care
- home care
- shared care
- transitional care
- annual review.
All patients should have access to a specialist CF Dietitian at all of these times. The same dietitians should provide inpatient and outpatient advice to ensure continuity of care and to prevent the important minutiae of care being overlooked. Advances in telecommunications and technology allow opportunities to re-evaluate service delivery.
6.5. Key considerations of service provision
A clear discharge plan and follow-up arrangements should be provided for patients treated in hospital, especially for those requiring ongoing nutritional support.
6.5.2. Home treatment
For those being treated with intravenous antibiotic therapy at home, there should be access to a specialist CF Dietitian at the start and end of this treatment, with ongoing nutritional support provided remotely (e.g. by telephone, telemedicine) or via the CF Clinical Nurse Specialist. There should be clear channels of communication between the CF Clinical Nurse Specialist and the specialist CF Dietitian.
6.5.3. Outpatients with CF-related diabetes
Outpatients with CF-related diabetes should have access to a specialist CF Dietitian with experience in the management of this CF complication.
6.5.4. Shared care
In general, due to the complexity of the dietetic needs of adults with CF, shared care is not appropriate. In paediatric Centres there should be:
- protocols for the delivery of care and lines of responsibility for nutritional management
- an identified dietitian within the shared care hospital who will liaise with the specialist CF Dietitian at the Centre
- review of all patients by the Centre's specialist CF Dietitian at least twice a year.
The paediatric and adult specialist CF Dietitians should work together to promote autonomy, facilitate self-management and ensure a smooth transition. At the time of transfer, the paediatric specialist CF Dietitian should provide a clear and concise summary of the nutritional management and challenges for each patient. Where possible the paediatric specialist CF Dietitian should provide a written treatment plan.
7. Framework for microbiology
A Clinical Microbiologist with specialist knowledge of CF infection should be part of the CF MDT. This individual may be a medically trained clinical microbiologist/infectious disease specialist; alternatively, a clinical scientist with relevant knowledge and experience may be able to undertake this role. The CF Clinical Microbiologist should work closely with the microbiology laboratory providing diagnostic services for the CF MDT and also with the local infection control and prevention team.
In order to provide support to the CF MDT for the diagnosis and treatment of infection, the CF Clinical Microbiologist needs to know about the range of infections in CF. In particular, they need to be aware of the role of unusual micro-organisms, the risk of cross infection and the impact of long-term chronic infection on microbiological laboratory testing and treatment. In addition to a good basic knowledge, the CF Clinical Microbiologist should have evidence of CPD in CF microbiology and attend specialist CF meetings and conferences.
7.1. The role of the CF Clinical Microbiologist
The CF Clinical Microbiologist should ensure that appropriate laboratory microbiology provision is in place. The individual may be part of the management of the laboratory. Alternatively, these services may be provided through an external contract, in which case the CF Clinical Microbiologist should be involved with setting the terms of the contract and act as an advocate for the CF Centre.
The CF Clinical Microbiologist should advise on the diagnosis and treatment of infection including the monitoring of antibiotics. This may be achieved by attendance at the CF MDT meetings. The CF Clinical Microbiologist should also act as an advisor on infection prevention and control in the CF Centre. This may be delegated to the designated infection control doctor if such a position exists.
7.2. Overview of laboratory services
The CF Clinical Microbiologist should ensure that the full range of microbiology laboratory tests needed for the CF Centre is available and that the laboratory service provided is based on published guidelines , , and . The laboratory should be fully accredited by a recognized national scheme for clinical microbiology and should participate in external quality assurance, which includes CF-associated pathogens. There should be provision to send relevant samples to a reference laboratory specializing in CF microbiology when required.
The laboratory should provide accurate and timely results to the CF Centre with an agreed system for notifying urgent and important results. The technical staff in the laboratory should have sufficient expertise and knowledge to deal with the complex microbiology of CF infections.
There should be a framework for recording and investigating errors and other incidents, with evidence of how the lessons learned are used to inform a programme of service improvement.
The service should be regularly audited. Examples of audits are the turn-around time (i.e. the time between the receipt of the sample in the laboratory and the time when the result is available to the CF MDT), the accuracy of identification and susceptibility testing, and the appropriate and prompt communication of urgent results to the CF MDT.
7.3. Clinical microbiology services and the CF MDT
The following items should be agreed between the CF MDT and the clinical microbiology service.
- Which respiratory samples should be taken and how should they be processed (e.g. sputum, bronchoalveolar lavage, cough swab or a pharyngeal swab).
- Which samples should be taken for the diagnosis of an infected intravascular line.
- Diagnosis of other infections including infections of the gut (e.g. enteric viruses, when and how to test for toxigenic Clostridium difficile)
- The level of identification of micro-organisms (e.g. genus, species, subtype) required in individual cases. This may include a discussion on the tests that can be performed in a local laboratory and what may need to be referred to a specialist laboratory with more advanced testing methodology (e.g. confirmation of first infection with Burkholderia spp. with accurate species identification).
- Typing methods and frequency of typing (i.e. how often the CF MDT should send samples for routine surveillance and when additional typing should be done due to suspicion of cross infection)
- Measurement of antipseudomonal antibodies where appropriate
- Provision of diagnostic testing for fungal and mycobacterial infection together with level of identification and role of typing
- Susceptibility testing — agreement on the antibiotics to be tested and when susceptibility testing is helpful
- Virology services should include rapid identification of highly pathogenic viruses that may spread between patients — both familiar (e.g. influenza virus) and emerging viral pathogens (e.g. SARS, MERS coronavirus).
- Which results need to be phoned urgently to the CF MDT (e.g. first growth of Pseudomonas aeruginosa, new isolation of Burkholderia cepacia complex and other Burkholderia species, MRSA, possible Mycobacteria seen in sputum).
- Advice on infection prevention and control.
In addition, a robust framework for communication between the microbiology services and the CF MDT should be agreed (e.g. telephone contact, ward rounds to review patients, participation in MDT meetings).
7.4. Clinical advice on treatment of infection
The CF Clinical Microbiologists should work with the CF MDT to draw up guidelines for the use of antimicrobials, including the selection of treatment for clearance of new infections, therapy for acute exacerbation and long-term suppressive antibiotics. The aim is to reduce morbidity and hospital admissions and to use antibiotics responsibly in order to limit the development of resistance.
There must be provision of therapeutic drug monitoring of antibiotics. The CF Clinical Microbiologist should ensure that guidelines and advice are available on the maintenance of optimum antibiotic levels in the patient in order to promote effective treatment while minimizing side-effects.
7.5. Infection prevention and control
The CF Clinical Microbiologist should work with the CF MDT and the local infection control team to develop a local infection control and prevention policy and procedures in line with expert national and international guidelines , , , , and . This policy should include:
- how patients with transmissible infections are managed, both in the community and in hospital, in order to prevent the spread of infection
- surveillance for transmissible infection (e.g. how often to screen and which samples to send to the laboratory)
- antimicrobial treatment to clear carriage of potentially transmissible micro-organisms
- guidelines for staff with infections
- the investigation of outbreaks
- the provision of facilities for the CF Centre and the outpatient department — this should include the cleaning and maintenance of equipment and involvement in any plans for refurbishment or re-build of the department.
7.6. Role in clinical research and data collection
CF Clinical Microbiologists can have an active role in CF clinical research. They may be involved with the design of innovative research but also have a role in the provision of reliable and accurate laboratory support for clinical studies. They can also help to ensure that accurate microbiological results are available for national and international database collection.
8. Framework for medicines management
Optimal care of people with CF requires complex multidrug treatment plans. These drugs may be administered by oral, intravenous and inhaled routes. Adverse effects and drug interactions are common.
Many of the drugs are expensive and require specialist assessment and instruction on optimal administration. Adherence is a major challenge for patients and parents/carers. Non-adherence is associated with poor outcomes. CF Centres must have an effective medicines management programme to support patients in optimizing their therapy. The CF Clinical Pharmacist is pivotal in this process  . In European countries, decentralized clinical services, with a pharmacist working in the ward at least 50% of his/her time, or with pharmacists visiting wards daily, are not very common  . Only two countries, UK and Ireland, have developed these clinical services to a significant extent  .
8.1. The role of the CF Clinical Pharmacist
CF Clinical Pharmacists have a central role in managing medicines effectively  . The overall goal of clinical pharmacy activities is to promote the correct and appropriate use of medicinal products and devices  . These activities aim to:
- maximize the clinical effect of medicines (i.e. using the most effective treatment for each patient)
- minimize the risk of treatment-induced adverse events (i.e. monitoring the therapy course and the patient's compliance with therapy)
- optimize the expenditures for pharmacological treatments borne by the national healthcare systems and by the patients.
The principle objective of the service provided by the CF Clinical Pharmacist is to provide patient-focused pharmaceutical care, defined as the responsible provision of medication to achieve definite outcomes that improve patients' quality of life and long-term survival. The service is the process through which the pharmacist cooperates with a patient and other healthcare professional in designing, implementing and monitoring a therapeutic plan to produce these specific health outcomes  .
Effective provision of a clinical pharmacy service to the CF Centre relies on the knowledge and skills of a CF Clinical Pharmacist and the quality of various support services, such as a medicine information service with experience in the problems of CF and paediatrics (if applicable), and the necessary procurement and distribution services that can provide an efficient medicine supply service for inpatients. A dispensing service should also be provided as required. Access to an on-call service for the supply of urgent medication, information and advice for inpatient care, and an aseptic dispensing service for the preparation of intravenous antibiotics including complex desensitization regimens should also be available.
The CF Clinical Pharmacist should:
- dispense medications to inpatients or outpatients as required in their institution
- attend CF wards rounds and CF MDT meetings
- support and provide information to other pharmacists in the department who may not be familiar with CF
- liaise with paediatric and adult Centres during transition of care and transfer of patients
- support and provide information to pharmacists working in primary care and other hospitals
- maintain CPD through appropriate study and attendance at relevant study days, and at national and international conferences
- network with other CF Pharmacists for advice and CPD.
8.2. Pharmaceutical care practice for CF Clinical Pharmacists
8.2.1. Managing formularies, clinical guidelines and treatment protocols
The CF Clinical Pharmacist should assist in the completion of formulary applications to ensure that the appropriate medicines are introduced into clinical practice. They should also assist in the development and support of homecare services, such as home intravenous antibiotics, and manage and monitor the delivery of medication in this setting.
Effective communication should exist between the CF Clinical Pharmacist and other members of the CF MDT. As for all clinical professionals in the CF MDT, the Clinical Pharmacist should participate in CPD and attend CF conferences and relevant study days. They should also contribute to education and training of other healthcare professionals, including those working in primary care, as appropriate. The CF Clinical Pharmacist should act as an advisor on the legal and ethical responsibilities of using medicines, including sourcing and administration of unlicensed and off-label medicines. Any problems with medication supply should be resolved by the CF Clinical Pharmacist and communicated to the CF MDT.
The CF Clinical Pharmacist may be required to collaborate with CF research and development and assist in the completion of individual funding requests or exceptional case requests for the supply of specific medications for individual patients where no such mechanism exists to currently fund that treatment.
8.2.2. Medication reconciliation/history taking
The CF Clinical Pharmacists is responsible for medicines reconciliation at admission/transfer from other institutions and on discharge, including alternative over-the-counter medications, trial medications and medications used for other conditions. They should ensure that an accurate history is recorded, including previous allergic reactions/adverse drug reactions.
8.2.3. Prescription monitoring and medication review service
In the monitoring and review of patient medication, the CF Clinical Pharmacists should ensure that medication and the formulation are appropriate for the patient, oversee extended prescribing for allied healthcare professionals including other pharmacists, and check for drug interactions. The CF Clinical Pharmacist is also responsible for ensuring that prescriptions are complete, unambiguous and legal, and for detecting potential medication errors.
8.2.4. Identifying patient and medication risk factors
It is the CF Clinical Pharmacist's responsibility to ensure that patient characteristics, including age, pregnancy or breast feeding, and organ dysfunction are taken into account when medicines are prescribed, and to check the response to previous and current medication. The use of non-drug and complementary therapies should also be taken into account when managing the patient's medication.
8.2.5. Preventing, detecting and reporting adverse drug reactions
The CF Clinical Pharmacist needs to document and report all reactions to newer medications and serious reactions to established medications to the appropriate national body. This includes documentation of individual toxicity/allergies/hypersensitivity reactions and contraindications, and monitoring for any adverse drug reactions. The appropriate use, storage and disposal of medicines should be ensured in order to minimize adverse events.
8.2.6. Individualizing drug and dosage requirements
The CF Clinical Pharmacist should aim, whenever possible, to maximize the therapeutic potential and minimize the adverse effects of medicines. Therapeutic drug monitoring of specific medicines (e.g. aminoglycosides, azoles) according to an individual's pharmacokinetic variables and monitoring and reviewing the outcome of an individual's need for medication are also required. While optimizing the use of medicines the CF Clinical Pharmacist also needs to take into account the patient's wishes and lifestyle.
The CF Clinical Pharmacist needs to keep up to date with newly available medications and therapies (e.g. new nebulized antimicrobials), and find a place for them in the treatment regimen.
8.2.7. Educating and counselling patients and carers
The CF Clinical Pharmacist has an important role to play in providing appropriate patient education and counselling to ensure the safe and effective use of medicines. This may include patient information leaflets about medicines and other appropriate methods of improving adherence to treatment. Pharmacists should also agree an informed plan with a patient/carer to achieve the best possible concordance with medication.
8.2.8. Evaluating medicine use
The CF Clinical Pharmacist's non-clinical responsibilities will include financial reporting to the CF MDT, hospital management, and other authorities, as appropriate, on CF medication usage. They should audit treatment guidelines, new therapies and homecare services.
9. Framework for psychosocial care
Living with CF provides many challenges for patients and their families. The CF Centre should provide adequate psychosocial care and support to help the person with CF and the families meet these challenges. In order to deliver optimal care CF Centres need a multidisciplinary framework to include access to psychosocial professionals throughout the patient's life. The core psychosocial professionals available should be a Clinical Psychologist and a Social Worker, though variations on these professions are acceptable provided core competencies are met (see below). Psychosocial professionals should be proficient in the following areas: working with children, families and adults according to the needs of the specific CF Centre; working with patients presenting with a range of clinical severity; and delivering care in all CF settings including outpatients, inpatients, community and residential care.
The variability of patient needs and availability of expertise in CF Centres prevent the formulation of a single programme. Psychosocial care should be provided within the context of the patients' development: from infancy to toddler, childhood, adolescence, young adulthood, adult life and old age. In each stage there are age-related themes as well as CF themes  and  ( Table 3 ). Key stages include the time around diagnosis  , the transition to adult care , , , , , and  and the transition to end-of-life/transplantation care  and . The disease trajectory itself also necessitates times of increased psychosocial support, for example, at diagnosis, first P. aeruginosa infection, first inpatient admission, diagnosis of CF-related diabetes, the need for gastrostomy tube feeding, supplementary oxygen, non-invasive ventilation, and assessment for lung transplantation. Psychosocial professionals should be included in the multidisciplinary care at all of these stages ( Table 3 ).
Childhood years Adolescent years Adult years Starting kindergarten/day care/pre-school Starting secondary school Starting higher education Starting school Being a teenager with CF Starting to work First awareness of being different First relationship Starting a long-term relationship Eating problems First sexual experience Parenthood Sleeping problems Death of a CF friend Death of a CF friend Behavioural problems (e.g. non-adherence) Behavioural problems (e.g. non-adherence) Behavioural problems (e.g. non-adherence) Examples of key medical stages CF diagnosis Diagnosis of infertility First Pseudomonas infection Treatment of infertility First episode of allergic bronchopulmonary aspergillosis Awareness of deteriorating disease Gastrostomy placement Transition to the adult clinic Diagnosis CF-related diabetes Transition to transplantation First haemoptysis and other complications Transition to end-of-life care Supplementary oxygen dependence Transplantation
CF, cystic fibrosis.
9.1. The CF social worker
The CF Social Worker provides expertise in helping patients and families with their emotional and practical needs and supports patients and families in coping with CF in the different developmental and disease stages. The CF Social Worker should bridge the gap between hospital life and home life and liaise with locally available support so that local services can be accessed. The CF Social Worker is actively involved in the different transition stages, including transition to adult care and transition to transplantation care ( Table 3 ). The CF Social Worker has an expertise that complements that of the CF Clinical Psychologist.
The CF Social Worker must have skills in the assessment of practical needs and provide a range of services that are available in the patient's country. Up-to-date knowledge of the country's system of benefits and allowances is essential. The CF Social Worker has to be able to liaise with other agencies (e.g. health insurance companies, child benefit agencies, social welfare agencies, hospital administration, school, CF patient associations) and serve as an advocate for patients and families. The CF Social Worker must have expertise in educational and career issues of the country where the patient resides. They should be skilled in the implementation of child protection procedures, and ensure effective information sharing, referral and liaison to home authority teams, where appropriate. Home visits can greatly contribute to best care and should be available where needed.
9.1.2. Professional development
CF Social Workers need to keep up to date with changes in healthcare systems, financial or social security matters, educational and work aspects, and patient and family welfare concerns. CF Social Workers need continuous education about CF issues. They should attend national and international conferences regularly to maintain up-to-date knowledge about CF and new scientific developments.
9.2. The CF Clinical Psychologist
During their life people with CF have to acquire specific CF-related healthcare behaviours in conjunction with acquiring normal developmental tasks. The CF Clinical Psychologist can help patients and families with these challenges and support them in coping with CF and its treatment throughout life.
In relation to the patient and the family, the key responsibilities of the CF Clinical Psychologist are the assessment of, and intervention in, emotional, behavioural and psychological difficulties, using evidence-based treatments where indicated and making onward referrals where appropriate. The CF Clinical Psychologist is responsible for all the psychological work in the CF Centre. They should offer outpatient clinics as well as caring for hospitalized patients. Adherence, eating behavioural problems, anxiety and depression, demoralization, pain, phobias and sleep are day-to-day themes that need psychological care.
The CF Clinical Psychologist may use mediation techniques in working with other CF MDT members. In addition, the CF Clinical Psychologist should provide a consultation and supervision service to other members of the CF MDT in their work with patients, and provide staff support in coping with ‘working in CF’.
The CF Clinical Psychologist must be registered with their national governing body. They should have expertise in child/adolescent and/or adult clinical psychology and also in systemic psychology and the psychology of grief and bereavement. The CF Clinical Psychologist must be skilled in applying therapeutic techniques that have proven efficacy in patients and families with CF. These include, for example (cognitive) behavioural techniques  and  and motivational interviewing  . Finally, the CF Clinical Psychologist has to be up to date with research on psychological issues in CF, including adherence, self-management and self-care, impact of chronic illness on human development, impact of chronic illness on family and social life, end-of-life issues and palliative care. The CF Clinical Psychologist should have or should develop, skills and experience in conducting psychological research with the aim of improving the care of patients and the understanding of psychosocial issues in CF.
9.2.2. Professional development
CF Clinical Psychologists have a responsibility to engage in CPD and in some countries this will be assessed as part of annual registration. Clinical Psychologists working in CF have a responsibility to update their knowledge of medical aspects of CF as well as mental health. Some countries have a national body for psychosocial professionals, such as in the UK, and membership is a requirement of practising in a CF team. CF Clinical Psychologists should attend national and international conferences regularly to maintain CF knowledge and to be aware of scientific developments.
9.3. Facilities and requirements for psychosocial care
The CF Clinical Psychologist and the CF Social Worker need sufficient time, office space, and facilities, and the support and respect of the CF MDT. The CF Social Worker and the CF Clinical Psychologist often need to stay in regular contact with patients and families in between clinic visits and therefore need access to modern media (e.g. email, phone, texting). They both need an up-to-date interactive referral system to external psychosocial professionals and institutions in order to provide problem-specific psychosocial/mental healthcare (e.g. for attention deficit hyperactivity disorder or autism) within the vicinity of a patient's home. The CF Clinical Psychologist and CF Social Worker must participate and contribute to the MDT meetings, decision making and patient consultation.
10. Framework for clinical genetics
Clinical Geneticists, Medical Molecular Genetic Laboratory Specialists and Genetic Counsellors have an increasingly important role in the complex diagnosis and disease management of CF, particularly in the areas of disease diagnosis, informed reproductive choices and the assessment of disease liability of CFTR variants detected by DNA sequencing. Furthermore, the Clinical Geneticist assesses the linkage phase through family segregation analysis, and ensures that complex alleles (which may be associated with variable CF phenotype) are not under- or misdiagnosed.
The Genetic Counsellor or the Clinical Geneticist provides counselling on reproductive options to the families of newly diagnosed children and to adult patients, and facilitates identification of at-risk family members who are genetically related to the patient.
Clinical Geneticists, working within the CF Centre, also coordinate data sharing with specialized registries (e.g. the ECFS Registry) and submission of detected CFTR mutations to both the Cystic Fibrosis Mutation Database (CFTR1), which serves as a locus-specific database for mutations and variants identified on a world-wide scale, and the Clinical and Functional Translation of CFTR online interactive resource (CFTR2), in order to objectively substantiate the disease liability of identified CFTR gene variants.
If administration of CFTR modulating therapies is considered, the CF Clinical Geneticist is responsible for the laboratory verification of the CFTR genotype in eligible patients (optimally by independent sampling and DNA sequencing) and that the laboratory examination is performed in an ISO 15189-accredited laboratory that assures appropriate turn-around time.
11. Framework for data collection
CF is a multisystem clinically heterogeneous disease with variable outcomes despite its monogenic origins. Although phenotypic variation is influenced by genotype, siblings with the same genotype differ in outcome suggesting the influence of other factors such as modifier genes, the environment, airway microbiota, social class, sex, access to healthcare and adherence to treatment  . Collecting data at a national and international level remains a key process to aid the understanding of the epidemiology and outcomes of the disease. It is only through accurate data collection that disease progression, outcomes, health economics and the need for change can be identified  . High-quality data can also be used by policy makers to focus on and prioritize future strategies and interventions.
CF is a relatively rare disease with small patient numbers. Collecting data from a single institution limits the level at which clinical and translational research can be undertaken, and does not capture the significant variability in geographical outcome  . It is therefore essential that both small and large CF units submit data at least annually to national and/or European CF registries in order to ensure that appropriate longitudinal data are collected. The registry also acts as a monitor for an individual Centre's outcomes, providing an additional tool for ensuring standards of care and appropriate clinical governance.
Healthcare professionals can find collecting and submitting data to national registries laborious and time consuming. Every effort should be made to ensure that data sets are limited to those of predictive value and that individuals can upload data through a secure intuitive interface. Funders must ensure that larger CF Centres have the resource to employ either a data clerk or alternative individual whose ring-fenced responsibilities include national data submission. To have value, such a person must have meaningful access to the management structure so that their voice counts and they can submit gold standard data.
There is a need for the international CF community to adopt a standard coding structure. Creating uniform clinical terminologies and classifications of disease through a primary coding structure would allow clinical data to be mapped and shared between registries as well as other data sets. The changes would result in a common digital language allowing effective international collaboration and would remove key barriers to electronic connectivity.
Addressing this issue is a matter of urgency, as a new era of medical informatics and electronic health records is upon us. Health services have started to successfully deploy electronic patient records, which automate the capture of data and have the potential to feed large continuous data sets directly into national and international registries. In Europe, a standard called XML has been adopted as a first step to harmonizing data from national registries. Almost all national organisations follow this initial standard, but this is only a first step in order to standardise the uploading; if the data collected do not adhere to common unequivocal definitions, the XML format cannot correct it. Therefore, common definitions and coding in both national registries and directly reporting individual centres are crucial.
The European Commission has decided to start funding a European Platform on Rare Diseases Registration, which will provide services and tools for the existing and future rare diseases registries, in accordance with the Council Recommendation on action in the field of rare diseases (2009/C 151/02).
The interconnectivity will maximize patient benefit for minimum outlay, which is a key given the difficult financial situation in healthcare. Adopting a detailed coded registry structure can have the added advantage of reducing costs and improving productivity  and . All such European and/or international data aggregations will have to make the best possible use of local/regional/national data acquisition and storage and intelligent ways of data sharing or retrieval will have to be developed.
Registries are here to stay and should be seen as a key part of any chronic disease management.
12. Challenges relating to developing health services in low income countries
The aim of the ECFS Standards of Care Guidelines is to improve the quality of care for patients with CF and to establish best practice across the whole of Europe. Immediate implementation of these guidelines may prove difficult for less economically advantaged countries where CF services are absent or inadequate. The EU EuroCareCF European Commission 6th Framework Coordination Action project identified a persisting wide difference in the standards of care across Europe, with some Eastern European countries having very basic or no recognizable CF services  . The likely reason for such dramatic inequalities has been the absence of appropriate funding, a lack of staff recruitment and training, and also a lack of political prioritization.
The current situation in Eastern Europe was assessed from the responses to a questionnaire distributed to most Eastern European countries by the ECFS Standards of Care Committee. The aims were to evaluate:
- a minimum number of patients who attend CF Centres in Eastern Europe
- national recognition of CF Centre networks, and
- the composition of CF MDTs and the cooperation between paediatric and adult Centres.
Each question was answered on the basis of the current situation in the country and in relation to the ECFS Standards of Care  . The response rate was 44% (7/16: Czech Republic, Hungary, Latvia, Poland, Serbia, Slovakia, Ukraine).
The major observations were as follows. While the number of patients per CF Centre is currently below 50 in some Eastern European countries, a requirement for a minimum number of 50 was seen to be an achievable goal. Centralized CF care has been endorsed by government authorities in only three of seven Eastern European countries. A paediatrician/pulmonologist, a physiotherapist and a CF nurse specialist were agreed to be essential team members. Many CF Centres lack a full-time CF nurse specialist, a dietitian, a microbiologist, a psychologist, a social worker or secretarial support. Collaboration between paediatric Centres and those for adults with CF had not been established in two of the countries that replied to the survey.
It is imperative that all European countries should strive to implement best practice in accordance with the ECFS recommendations. An initial stepwise approach may be needed in some low income countries where there are no established services and CF MDTs virtually do not exist. For example, initial recruitment of core medical, nursing and physiotherapy staff may be the most appropriate initial investment on the way to establishing a service that meets all ECFS standards. It is no longer acceptable to have such dramatic variation in the survival of people with CF across European nations, and every effort must be made to deliver equality and high standards of care.
CF care in low income countries should be centralized in well-established CF Centres that can guarantee a reasonable standard of complex care for both paediatric and adult patients. The Centre should care for at least 100 patients, although a minimum of 50 may be temporarily considered acceptable. Because of the financial and staffing limitations in Eastern Europe, shared care with local hospitals is not a preferred model of care. Resources should be directed at establishing state-of-the-art CF care at a national level by the development of specialized CF Centres at major hospitals, and where possible at the level of University Hospitals. The minimum staff requirements for a specialist CF team include a physician and a specialist nurse (one each for children and adults in Centres that care for all age groups), and a CF specialist physiotherapist. The goal is to develop teams that include a microbiologist, dietitian, psychologist, social worker and clinical geneticist. Meanwhile the absence of these specialists should not delay the setting up of regional CF Centres. Their roles may be temporarily performed by specialist consultants of the hospital who can be accessed by the CF service, even though not primarily allocated to a CF team and therefore not able, for instance, to participate in regular CF MDT meetings.
13. Perspective from European CF associations
13.1. The function and role of national CF patient organisations in Europe
Most European countries have their own national CF patient organisation. These vary in size and methodology but have one thing in common: they fight for the interests of people with CF, in the broadest sense of the word. They work together with volunteers, who are often experts in CF but who may be non-medical. In Europe patient organisations are developing their own in-house expertise and employing professional staff, for example in the area of healthcare quality, scientific research, communication, fund raising, information provision, and the legal and psychosocial aspects of CF. The organisations aim to support patients and their parents, both individually and collectively, and to define research agenda, to finance scientific research and to test healthcare quality. They are often closely involved in the setting up and maintenance of guidelines for the diagnosis and treatment of CF.
The national CF organisation can play an important role in the national CF registry. Many have helped found these registries and continue to support and finance them. In a number of countries, the CF organisation plays a role in the set-up and organisation of research networks and healthcare quality improvement programmes for people with CF.
Fund raising is an important prerequisite to enable the organisations to successfully achieve the above aims. Over the past few years, CF organisations in countries such as the UK, Germany, Belgium, France, Italy and The Netherlands have invested millions of Euros in scientific research and healthcare quality. As a result, they have made important contributions to the progress that has been made in many healthcare areas of CF.
Patient participation is an important part of the work achieved by patient organisations, as it is exactly the patients' perspective that can and should be expressed by the national CF organisations.
13.2. National organisations
The national CF organisations have responsibilities to provide information. This material, which is made available to people with CF and their parents/carers, is often developed in collaboration with the CF Centres and covers all aspects of life with CF: diagnosis, treatment, growing up with CF, raising a child with CF, going to school with CF and building a life with CF. National CF groups should work closely with CF Centres in the organisation of healthcare, a cooperation that may vary in its infrastructure in different countries. However, in all cases, representatives of those Centres should be present on medical advisory boards and scientific councils.
CF organisations should organise meetings for parents and, with the use of information technology to safeguard against cross-infection risks, for the patients themselves. E-health has many advantages and is a subject that is being researched and developed.
CF organisations are the obvious parties to represent and protect the interests of patients and their parents/carers, for example by supporting ready availability of new medications, securing reimbursements for medication and access to high-quality healthcare. CF organisations should lobby and exert pressure on the authorities, government and insurance companies in this regard. They should also organise congresses, symposia and other meetings (in collaboration with or under the supervision of the healthcare organisations), in which the specific (scientific) aspects of CF are discussed.
CF patient organisations are non-medical yet through close cooperation with CF Centres have developed a lot of CF expertise. It is important that the Centres and the organisation exchange information on a regular basis in order to facilitate a proactive approach to developments in the healthcare industry and scientific research. This collaboration will help to improve communication with patients, facilitating their inclusion in scientific studies and solving problems on a national level more swiftly.
13.3. European organisations
The European CF patient organisations are united in a single European society — CF Europe (CFE). The importance of collaboration in Europe is growing, especially with regard to healthcare access, which is not uniform, or even available, in all European countries. As a result, collaboration in the fields of research, research financing and fund raising is continually increasing.
The European collaboration should lead to the CF organisations in countries where CF healthcare is already at a high level accepting their responsibility and offering their expertise to countries in which adequate healthcare, access to healthcare and the ready availability of medication are not universal. This should take place in close collaboration with the CF Centres. Collaboration through CF Europe has made it easier to lobby effectively on a European level with regard to subjects such as organ donation, accessibility, quality and affordability in healthcare.
Another level of European collaboration is partnering with the European overarching patient support organisation (Eurordis), which is representing the majority of rare disease national and regional organisations (including CF) in e.g. terms of awareness building, access to care, reimbursement policies, development of European guidelines for centre care fundraising, introduction of orphan medicinal products into therapy, including training courses on various aspects of patient advocacy.
CF patient organisations are working increasingly with the ECFS, for example by participating in the executive boards of the EFCS Patient Registry and the EFCS Clinical Trials Network. The latter is financially supported by a number of patient organisations. Through the CF patient organisations, patients and parents have become more involved recently in the assessment of the ECFS Clinical Trials Network research protocols.
Conflict of interest
S. Conway, K. De Rijcke, P. Drevinek, J. Foweraker, T. Havermans, H. Heijerman, L. Lannefors, A. Lindblad, M. Macek, S. Madge, M. Moran, L. Morrison, A. Morton, J. Noordhoek, D. Sands, A. Vertommen, and D. Peckham have no conflicts of interest to report. I. M. Balfour-Lynn declares personal fees from Vertex, outside the submitted work.
We would like to thank Drs Preston Campbell, Carla Colombo, Ed McKone, Anil Mehta, Hanne Olesen and Thomas Wagner for their advice and Mrs Tina Payne-Gath for administrative support.
-  J.A. Dodge, P.A. Lewis, M. Stanton, J. Wilsher. CF mortality and survival in the UK: 1947–2003. Eur Respir J. 2007;29:522-526
-  R. Mahadeva, K. Webb, R.C. Westerbeek, N.R. Carroll, M.E. Dodd, D. Bilton. Clinical outcome in relation to care in Centres specialising in cystic fibrosis: cross sectional study. BMJ. 1998;316:1771-1775
-  C. Johnson, S.M. Butler, M.W. Konstan, W. Morgan, M.E. Wohl. Factors influencing outcomes in cystic fibrosis. A center-based analysis. Chest. 2003;123:20-27
-  E. Kerem, S. Conway, S. Elborn, H. Heijerman, for the Consensus Committee. Standards of care for patients with cystic fibrosis: a European consensus. J Cyst Fibros. 2005;4:7-26
-  S.C. Bell, P.J. Robinson. Cystic fibrosis standards of care Australia. D.S. Fitzgerald (Ed.) (Cystic Fibrosis Australia, Sydney, NSW, 2008)
-  Standards for the clinical care of children and adults with cystic fibrosis in the UK. 2nd ed. (Cystic Fibrosis Trust, London, 2011) [ https://www.cysticfibrosis.org.uk/media/82070/CD_Standards_of_Care_Dec_11.pdf ]
-  C. Colombo, J. Littlewood. The implementation of standards of care in Europe: state of the art. J Cyst Fibros. 2011;10(Suppl. 2):S7-S15
-  R. Loddenkemper, P.L. Haslam, T. Séverin, I. Annesi-Maesano, A. Chuchalin, C. Coles, et al. European curriculum recommendations for training in adult respiratory medicine: report of the HERMES Task Force. European Respiratory Society. Breathe. 2008;5(1):80-93
-  S. Madge, K. Khair. Multi-disciplinary teams in the United Kingdom: problems and solutions. J Pediatr Nurs. 2000;15(2):131-134
-  S.L. Madge. National consensus standards for nursing children and young people with cystic fibrosis. Paediatr Care. 2002;14(1):32-35
-  D.E. Geller, S.L. Madge. Technological and behavioural strategies to reduce treatment burden and improve adherence to inhaled antibiotics in cystic fibrosis. Respir Med. 2011;105(Suppl. 2):S24-S31
-  S. Madge. Challenges for nurses. A. Bush, E.W.F.W. Alton, J.C. Davies, U. Griesenbach, A. Jaffe (Eds.) Cystic fibrosis in the 21st century in: Progress in respiratory research. vol. 34 (Karger, Basel, 2006) 286-292
-  S. Madge. Growing up and growing older with cystic fibrosis. J R Soc Med. 2006;99(Suppl. 46):23-26
-  D.R. Bolyard. Sexuality and cystic fibrosis. MCN Am J Matern Child Nurs. 2001;26:39-41
-  S. Roberts, P. Green. Sexual health of adolescents with cystic fibrosis. J R Soc Med. 2005;98(Suppl. 45):7-16
-  R.P. Arias Llorente, C. Bousono Garcia, J.J. Diaz Martin. Treatment compliance in children and adults with cystic fibrosis. J Cyst Fibros. 2008;7:359-367
-  S.Z. Nasr. Cystic fibrosis in adolescents and young adults. Adolesc Med. 2000;11:589-603
-  S. Madge, M. Bryon. A model for transition of care in cystic fibrosis. J Pediatr Nurs. 2002;17:283-288
-  P.A. Flume, L.A. Taylor, D.L. Anderson, S. Gray, D. Turner. Transition programs in cystic fibrosis centers: perceptions of team members. Pediatr Pulmonol. 2004;37:4-7
-  M. Bryon, S. Madge. Transition from paediatric to adult care: psychological principles. J R Soc Med. 2001;94(Suppl. 40):5-7
-  P.A. Flume, J.R. Yankaskas, M. Ebeling, T. Husley, L.L. Clark. Massive hemoptysis in cystic fibrosis. Chest. 2005;128:729-738
-  P.A. Flume, C. Strange, X. Ye, M. Ebeling, T. Husley, L.L. Clark. Pneumothorax in cystic fibrosis. Chest. 2005;28:720-728
-  A.D. Mackie, S.J. Thornton, F.P. Edenborough. Cystic fibrosis-related diabetes. Diabet Med. 2003;20:425-436
-  K. Lowton. ‘A bed in the middle of nowhere’: parents' meanings of place of death for adults with cystic fibrosis. Soc Sci Med. 2009;69:1056-1062
-  D. Sands, T. Repetto, L.J. Dupont, A. Korzeniewska-Eksterowicz, P. Catastini, S. Madge. End of life care for patients with cystic fibrosis. J Cyst Fibros. 2011;10:S37-S44
-  International Physiotherapy Group for Cystic Fibrosis (IPGCF). Physiotherapy for people with cystic fibrosis: from infant to adult. 4th ed. (, 2009) [ http://www.ecfs.eu/ipg_cf/booklet ]
-  C. Darquanne. Aerosol deposition in health and disease. J Aerosol Med Pulm Drug Deliv. 2012;25(3):140-147
-  B.M. Button, B. Button. Structure and function of the mucus clearance system of the lung. Cold Spring Harb Perspect Med. 2013;3(8) [pii: a009720]
-  C.P. van der Schans, A. Prasad, E. Main. Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis. Cochrane Database Syst Rev. 2000;210.1002/14651858.CD001401 [CD001401]
-  L. Lannefors, B.M. Button, M. McIlwaine. Physiotherapy in infants and young children with cystic fibrosis: current practice and further developments. J R Soc Med. 2004;97(S44):8-25
-  E. Main, A. Prasad, C.P. van der Schans. Conventional chest physiotherapy compared to other airway clearance techniques for cystic fibrosis. Cochrane Database Syst Rev. 2005;110.1002/14651858.CD002011.pub2 [CD002011]
-  M. Elkins, A. Jones, C.P. van der Schans. Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis. Cochrane Database Syst Rev. 2006;210.1002/14651858.CD003147.pub3 [CD003147]
-  J. Bott, S. Blumenthal, M. Buxton, S. Ellum, C. Falconer, R. Garrod, et al. Guidelines for the physiotherapy management of the adult, medical, spontaneously breathing patient. Thorax. 2009;64(Suppl. 1):i1-i51
-  L. Morrison, J. Agnew. Oscillating devices for airway clearance in people with cystic fibrosis. Cochrane Database Syst Rev. 2009;110.1002/14651858.CD006842.pub2 [CD006842]
-  A.E. Holland, B.M. Button, on behalf of the International Physiotherapy Group for Cystic Fibrosis. Physiotherapy for cystic fibrosis in Australia: knowledge and acceptance of the consensus statement recommendations. Respirology. 2013;18:652-656
-  N.A. McKoy, I.J. Saldanha, O.A. Odelola, K.A. Robinson. Active cycle of breathing technique for cystic fibrosis. Cochrane Database Syst Rev. 2012;1210.1002/14651858.CD007862.pub3 [CD007862]
-  E. Main. Airway clearance research in CF: the ‘perfect storm’ of strong preference and effortful participation in long-tem, non-blinded studies. Thorax. 2013;68:701-702
-  R.B. Parasa, N. Maffulli. Musculoskeletal involvement in cystic fibrosis. Bull Hosp Jt Dis. 1999;58:37-44
-  R. Tattersall, M.J. Walshaw. Posture and cystic fibrosis. J R Soc Med. 2003;96(S43):18-22
-  P.A. Nixon, D.M. Orenstein, S.F. Kelsey, C.F. Doershuk. The prognostic value of exercise testing in patients with cystic fibrosis. N Engl J Med. 1992;327:1785-1788
-  J.M. Bradley, F. Moran. Physical training for cystic fibrosis. Cochrane Database Syst Rev. 2008;110.1002/14651858.CD002768.pub2 [CD002768]
-  S.M. Paranjape, L.A. Barnes, K.A. Carson, K. v Berg, H. Loosen, P.J. Mogayzel Jr. Exercise improves lung function and habitual activity in children with cystic fibrosis. J Cyst Fibros. 2012;11:18-23
-  H.G. Heijerman, W. Bakker, P.J. Sterk, J.H. Dijkman. Oxygen-assisted exercise training in adult cystic fibrosis patients with pulmonary limitation to exercise. Int J Rehabil Res. 1991;14:101-115
-  K.G. Henke, J.A. Regnis, P.T. Bye. Benefits of continuous positive airway pressure during exercise in cystic fibrosis and relationship to disease severity. Am Rev Respir Dis. 1993;148:1272-1276
-  A.E. Holland, L. Denehy, G. Ntoumenopoulos, M.T. Naughton, J.W. Wilson. Non-invasive ventilation assists chest physiotherapy in adults with acute exacerbations of cystic fibrosis. Thorax. 2003;58:880-884
-  F. Moran, J.M. Bradley, A.J. Piper. Non-invasive ventilation for cystic fibrosis. Cochrane Database Syst Rev. 2013;410.1002/14651858.CD002769.pub4 [CD002769]
-  F. Moran, J.M. Bradley, L. Boyle, J.S. Elborn. Incontinence in adult females with cystic fibrosis: a Northern Ireland survey. Int J Clin Pract. 2003;57:182-183
-  S.A. Prasad, I.M. Balfour-Lynn, S.B. Carr, S.L. Madge. A comparison of the prevalence of urinary incontinence in girls with cystic fibrosis, asthma, and healthy controls. Pediatr Pulmonol. 2006;41:1065-1068
-  F.P. Edenborough, G. Borgo, C. Knoop, L. Lannefors, W.E. Mackenzie, S. Madge, et al. Guidelines for the management of pregnancy in women with cystic fibrosis. J Cyst Fibros. 2008;7:S2-S32
-  European Cystic Fibrosis Society. International Physiotherapy Group for Cystic Fibrosis. https://www.ecfs.eu/ipg_cf
-  L. Morrison, L. McIntosh, A. Freeman, on behalf of the Association of Chartered Physiotherapists in Cystic Fibrosis. ACPCF National Audit of Clinical Standards of Care in CF. (, 2010–2011)
-  C.C. Pedreira, R.G. Robert, V. Dalton, M.R. Oliver, J.B. Carlin, P. Robinson, et al. Association of body composition and lung function in children with cystic fibrosis. Pediatr Pulmonol. 2005;39:276-280
-  E.H. Yen, H. Quinton, D. Borowitz. Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis. J Pediatr. 2013;162:530-535
-  M. Stern, B. Wiedemann, P. Wenzlaff, on behalf of the German Cystic Fibrosis Quality Assessment Group. From registry to quality management: the German Cystic Fibrosis Quality Assessment project 1995–2006. Eur Respir J. 2008;31:29-35
-  G. Vieni, S. Faraci, M. Cillura, M. Lombardo, G. Traverso, S. Cristadoro, et al. Stunting is an independent predictor of mortality in patients with cystic fibrosis. Clin Nutr. 2013;32:382-385
-  J. Zhou, E. Garber, M. Desai, L. Saiman. Compliance of clinical microbiology laboratories in the United States with current recommendations for processing respiratory tract specimens from patients with cystic fibrosis. J Clin Microbiol. 2006;44:1547-1549
-  Laboratory standards for processing microbiological samples from people with cystic fibrosis, September 2010. Report of the UK Cystic Fibrosis Trust Microbiology Laboratory Standards Working Group 1st ed. (, September 2010) [ https://www.cysticfibrosis.org.uk/media/82034/CD_Laboratory_Standards_Sep_10.pdf ]
-  Atemwegsinfecktionen bei Mukoviszidose. in: Mikrobiologisch-infektiologische Qualitätsstandards. MiQ 24 (Qualitätssicherungskommission der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM), 2006)
-  Cystic Fibrosis Trust. Pseudomonas aeruginosa infection in people with cystic fibrosis. Suggestions for prevention and infection control 2nd ed. in: Report of the UK Cystic Fibrosis Trust Infection Control Group. (, November 2004)
-  Cystic Fibrosis Trust. Methicillin-resistant Staphylococcus aureus (MRSA). Report of the UK Cystic Fibrosis Trust Infection Control Group (, April 2008)
-  Cystic Fibrosis Trust. Antibiotic treatment for cystic fibrosis. Report of the UK Cystic Fibrosis Trust Antibiotic Working Group 3rd ed. (, May 2009)
-  L. Saiman, J. Siegel, the Cystic Fibrosis Foundation Consensus Conference on Infection Control Participants. Infection control recommendations for patients with cystic fibrosis: microbiology, important pathogens and infection control practices to prevent patient-to-patient transmission. Infect Control Hosp Epidemiol. 2003;24:S6-S52
-  Cystic Fibrosis Trust. The Burkholderia cepacia complex. Suggestions for prevention and infection control. Report of the UK Cystic Fibrosis Trust Infection Control Group 2nd ed. (, September 2004)
-  J. Redfern, K. Webb. Benefits of a dedicated cystic fibrosis pharmacist. J R Soc Med. 2004;97(Suppl. 44):2-7
-  R. Frontini, T. Miharija-Gala, J. Sykora. EAHP survey 2010 on hospital pharmacy in Europe: parts 4 and 5. Clinical services and patient safety. Eur J Hosp Pharm. 2013;20:69-73
-  A spoonful of sugar. Medicines management in NHS hospitals (The Audit Commission, London, 2001) [ http://www.audit-commission.gov.uk/SiteCollectionDocuments/AuditCommissionReports/NationalStudies/nrspoonfulsugar.pdf ]
-  European Society of Clinical Pharmacy. Clinical pharmacy overall goal. http://www.escpweb.org/cms/Clinical_pharmacy
-  UKCF Trust. Pharmacy standards of care. https://www.cysticfibrosis.org.uk/search.aspx?keywords=pharmacy%20standards (2011)
-  M.M. Ernst, M.C. Johnson, L.J. Stark. Developmental and psychosocial issues in cystic fibrosis. Child Adolesc Psychiatr Clin N Am. 2010;19:263-283
-  H. Oxley, A.K. Webb. How clinical psychologist manages the problems of adults with cystic fibrosis. J R Soc Med. 2005;98(Suppl. 45):37-46
-  I. Jedlicka-Köhler, M. Götz, I. Eichler. Parents' recollection of the initial communication of the diagnosis of cystic fibrosis. Pediatrics. 1996;97:204-209
-  D.L. Anderson, P.A. Flume, K.K. Hardy, S. Gray. Transition programs in cystic fibrosis centers: perceptions of patients. Pediatr Pulmonol. 2002;33:327-331
-  L.K. Tuchman, L.A. Schwartz, G.S. Sawicki, M.T. Britto. Cystic fibrosis and transition to adult medical care. Pediatrics. 2010;125:566-573
-  S.R. Patton, J.L. Graham, D. Holsclaw Jr., L. Varlotta. Survey of professionals' expectations of developmental task achievement of cystic fibrosis self-care in children. Pediatr Pulmonol. 2005;40:135-140
-  S.J. Towns, S.C. Bell. Transition of adolescents with cystic fibrosis from paediatric to adult care. Clin Respir J. 2011;5:64-75
-  D.S. Rosen. Transition of young people with respiratory diseases to adult health care. Paediatr Respir Rev. 2004;5:124-131
-  W.M. Robinson. Palliative and end-of-life care in cystic fibrosis: what we know and what we need to know. Curr Opin Pulm Med. 2009;15:621-625
-  G.S. Sawicki, E.J. Dill, D. Asher, D.E. Sellers, W.M. Robinson. Advance care planning in adults with cystic fibrosis. J Palliat Med. 2008;11:1135-1141
-  C.A. Glasscoe, A.L. Quittner. Psychological interventions for people with cystic fibrosis and their families. Cochrane Database Syst Rev. 2008;3 [CD003148]
-  C.M. Ward, T. Brinkman, K.J. Slifer, S.M. Paranjape. Using behavioral interventions to assist with routine procedures in children with cystic fibrosis. J Cyst Fibros. 2010;9:150-153
-  A.J. Duff, G.J. Latchford. Motivational interviewing for adherence problems in cystic fibrosis. Pediatr Pulmonol. 2010;45:211-220
-  J.M. Collaco, C.B. Morrow, D.M. Green, G.R. Cutting, P.J. Mogayzel Jr. Environmental allergies and respiratory morbidities in cystic fibrosis. Pediatr Pulmonol. 2013;48:857-864
-  G. Mehta, M. Macek Jr., A. Mehta. Cystic fibrosis across Europe: EuroCareCF analysis of demographic data from 35 countries. J Cyst Fibros. 2010;9(Suppl. 2):S5-S21
-  N. Shaw, D. Peckham, S. Conway, M. Denton. Financial savings following the introduction of a cystic fibrosis electronic. J Cyst Fibros. 2010;9:S116
-  C. Etherington, S. Conway, D. Peckham. The role of electronic patient records (EPR) in improving service efficiency and clinical performance in a regional adult UK centre. J Cyst Fibros. 2011;10:S96
a Paediatric and Adult CF Units, Leeds Teaching Hospitals Trust, UK
b Royal Brompton Hospital, Sydney Street, London, UK
c Cystic Fibrosis Europe, Belgium
d Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
e Department of Paediatrics, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
f University Hospital Motol, Prague, Czech Republic
g Department of Microbiology, Papworth Hospital NHS Foundation Trust, Papworth Everard, Cambridge, UK
h Cystic Fibrosis Centre, University Hospital Leuven, Belgium
i HagaZiekenhuis, Department of Pulmonology & Cystic Fibrosis, The Hague, The Netherlands
j Copenhagen CF Centre, Rigshospitalet, University Hospital, Copenhagen, Denmark
k Gothenburg CF Centre, Queen Silvia Children's Hospital, Göteborg, Sweden
l Department of Biology and Medical Genetics, University Hospital Motol, Prague, Czech Republic
m Second School of Medicine, Charles University Prague, Prague, Czech Republic
n Department of Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London, UK
o National Referral Centre for Adult Cystic Fibrosis, Pharmacy Department, St. Vincent's University Hospital, Ireland
p Gartnavel General Hospital, West of Scotland Adult CF Unit, Glasgow, UK
q Adult Cystic Fibrosis Unit, St James's Hospital, Leeds, UK
r Dutch Cystic Fibrosis Foundation, The Netherlands
s Department of Pediatrics, Institute of Mother and Child, Warsaw, Poland
t Cystic Fibrosis Centre, University Hospital Leuven, Belgium
u Adult Cystic Fibrosis Unit, St James's Hospital, Leeds, UK
© 2014 European Cystic Fibrosis Society., Published by Elsevier B.V.
European Cystic Fibrosis Society Standards of Care: Quality Management in cystic fibrosisMon, 08/18/2014 - 18:58
Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful treatments and patient outcomes to be recognized and improvement programmes to be implemented in specialist CF centres. Over the past decades, the greater volumes of data becoming available through Centre databases and patient registries led to the possibility of making comparisons between different therapies, approaches to care and indeed data recording. The quality of care for individuals with CF has become a focus at several levels: patient, centre, regional, national and international. This paper reviews the quality management and improvement issues at each of these levels with particular reference to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons.
Keywords: CF registries, Standards, Models of care, Quality management, Outcomes in CF.
Since the earliest days of cystic fibrosis (CF) treatment, detailed summaries of large clinical groups have been employed to determine and describe the best approach to treatment, based on improved outcomes  and . A comprehensive approach to therapy, routine monitoring, and attention to individual profiles and prognostic subgroups were highlighted in these early papers on CF management. The early years also included a cautionary tale, when mist tent therapy was cited as the key component responsible for remarkable survival in one large clinic, as documented in the newly established US CF Registry  and . Over the following decade, however, it became clear that the scientific evidence of a beneficial effect was lacking for mist tent therapy  . Nevertheless, the improved outcomes were real, and emphasis was eventually, and more appropriately, placed on the comprehensive management package, including early diagnosis, patient and parent education, frequency of patient visits, daily physical therapy and aggressive antibiotic therapy. It was also during this period that a new focus on growth and nutrition was evolving. Again, it began with reports from a large clinic where greatly improved outcomes were observed in patients with CF who were prescribed a high-fat diet in place of the historical low-fat diet  and . But it was only when the CF registry data for two large, university-based clinics with similar demographics and approaches to other aspects of treatment were compared that the possibility of a normal diet and the goal of normal growth in patients with CF were widely embraced  .
Although the benefits of specific treatments must be supported by evidence from well-controlled studies, there is great value in compiling and comparing outcomes in large clinical populations in order to document changes over time and to identify patterns and practices that may be associated with benefit or concern. Of particular importance are national registries that account for all, or a large and well-defined proportion of, CF patients in a region. National, annually updated CF registries in the USA since 1966  and Canada since 1970  were instituted primarily to describe population patterns of diagnosis, demographics and mortality. Over the years additional information was added to track important correlates of CF prognosis, such as lung function and growth. Near the turn of the century, the US CF registry began to compute centre-specific summaries, which allowed CF Centres to locate themselves in the range from low to high performance for several key measures. The CF Foundation (CFF) Quality Initiative  was launched to support Centres in a concerted effort to improve poor outcomes and emulate the successful strategies of Centres with consistently good outcome measures. Several European countries have established CF registries, as have Australia and New Zealand, and there is an ongoing effort to orchestrate a European CF registry combining existing national registries with data from countries without a registry  . The European Cystic Fibrosis Society Patient Registry  was founded in 2004 and was based on the entry of defined demographic and clinical data. Later demographic data from CF registries collected during the European 6th framework Coordination Action project (2006–2010) provided evidence on disparities in care between Western and Eastern European countries. By the beginning of 2013, 20 European countries participated, representing more than 18,000 patients with CF. Annual reports are available  , and the first comprehensive analysis has been carried out  .
Several quality management programmes have evolved, with Centre comparison as a primary motivation. Early registry development in Germany was called the Cystic Fibrosis Quality Assurance (CFQA) project  , and occurred long before the idea of publishing Centre-specific summaries was deemed acceptable in other regions. Whereas most registries report survival into the middle adult years, a report from South America  is a sobering reminder that attention to the quality and delivery of care is of primary importance.
As well as large Centre databases and national registries, there have been initiatives from the pharmaceutical industry to collect longitudinal data following large multicentre drug trials, to provide Phase IV analysis of treatment effects, and to study other prognostic factors. The Epidemiologic Study of Cystic Fibrosis (ESCF)  was a multicentre observational study that funded the collection of large amounts of clinical data on patients in participating Centres in the USA and Canada. The representativeness and continuity of the ESCF were complicated by funding issues, so that age and regional distributions and patterns over time were not always easy to interpret. But their analyses certainly intensified the interest in comparative studies and addressed many questions that will be more appropriately addressed by analysis of national registries, as more and more of them become poised to participate.
Issues of patient confidentiality and authorship in any publication must be addressed at an early stage of the planning of such studies. The equivalence of standard measures across populations, and even within populations, cannot be assumed and is another challenge in comparisons using registry data. The history and issues of benchmarking quality of CF care using registry data have been summarized in a recent review paper by Schechter  .
The ongoing Early Pseudomonas Infection Control (EPIC) study is an example of an observational study, supported in part and ‘at arm's length’ by the pharmaceutical industry, that combines registry follow-up with a study-targeted young American CF population. The study aims to answer specific questions about the early stages of the CF disease process and treatment options  . An Australian study of patients with CF identified at newborn screening highlights the difficulty of defining metrics for assessing progress, and by extension quality management, in the youngest patients  . Follow-up of well-defined groups of young patients with CF, especially those diagnosed by newborn screening, gives the best chance of describing and refining the best treatment practices  .
Effective quality management at all levels must recognize the contributions and the needs of all partners in the process, from the medical experts and care personnel, to the patient and family members, and the analysts and interpreters of results. The processes for provision of data and access to data must be transparent and audited regularly. There must be a balance between the process and proposed outcomes so that all Centres can participate at a level compatible with their size, funding and stage of development. Analysis of changes over time and region, with appropriate recognition of known and potential confounders, will provide knowledge and guidance for the continuing improvement of care and outcomes in CF.
Quality management is closely linked to the goal of quality improvement. Quality improvement in healthcare has been defined as ‘an interdisciplinary process to raise the likelihood of the delivery of best practices for preventive, diagnostic, therapeutic, and rehabilitative care to maintain, restore, or improve health outcomes of individuals and populations’  . Quality improvement is a science  and includes numerous distinct strategies for changing patient and provider behaviour, as well as redesigning systems of audit and feedback, case management, support for self-management, patient registries and computerized decision support  . But, the single, most basic approach involves iterative cycles of outcome measurement, identification of problems, implementation of potential solutions and repeated measurement  .
Quality management in CF takes place at different levels: patient, Centre, regional, national and international ( Fig. 1 ). The Dartmouth approach of systems embedded in systems acknowledges different levels of clinical care: the microsystem level involves the patient, their family and the specialist CF care team; the mesosystem level is the hospital/CF Centre in which the care is provided; and the macrosystem level includes healthcare organizations, networks and governance  . This paper reviews quality management issues at each of these levels.
2. Quality management at the patient level
2.1. Use of registry data
Patients are at the centre of all efforts to improve quality of care. This implies that they take an active part with CF teams in the continuous process of quality improvement. The use of CF registry data in daily care has been shown to be helpful in this respect , , , and . Classical outcome indicators describing nutritional status and lung function are shared with patients at the site of the visit  and are expected to help promote different strategies to improve quality of care, with positive consequences on quality of life and life expectancy.
2.2. Patient-centred approach
Patients are the subject of care, but also experts on life with CF and their expertise can complement that of the CF healthcare professionals. The patients and their family are involved in quality improvement at all levels and their collaboration is a fundamental prerequisite. Full respect, trust and transparency should exist between partners, with co-responsibility for success and compliance with treatment. There should be an openness and willingness to learn from each other.
Different steps are included in this quality improvement process. Electronic files based on appropriate software (e.g. Port-CF, MUKO.dok., ECFS Registry) are a necessary precondition. Appropriate data and follow-up parameters may be grouped or individually presented to show changes before and after therapeutic measures have been taken. These electronic files and follow-up charts may inform periodic CF team sessions and regular quality improvement conferences, centred on individual patients/parents.
International and national guidelines form the basis of different steps of therapy. Annual therapy goals can be set together with the patients/parents; therapy contracts may even be negotiated.
In the respiratory and nutritional fields, positive experiences highlight the successful implementation of quality improvement steps in CF patients and patient groups. For example, the natural progression in decline in forced expiratory volume in 1 s (FEV1)  and  can be counteracted by different therapeutic interventions, such as anti-infectious and anti-inflammatory therapy and also by emerging new treatments for subgroups of patients , , and . Adherence to pulmonary guidelines  , and education and training of physicians, families and patients  are successful quality improvement interventions that improve important outcomes. Key objectives are prevention and early treatment of exacerbations. For this, a patient checklist to be included in the electronic files is helpful to increase patient awareness of the early signs of exacerbation. Algorithms on what to do when FEV1 declines are an additional useful instrument and should also appear in the electronic files and be transparent to patients.
A similar experience has also been reported for nutritional interventions. Many patients do not follow nutritional guidelines and recommendations  and . This has a negative impact on the disease because adequate nutritional counselling, increased caloric intake and a good nutritional status are linked to favourable outcomes. In single cases an individually adapted strategy may be adequate. Quality improvement efforts have included individual and standardized nutrition plans and also behavioural and nutrition interventions to improve nutritional status in patients with CF  and .
Additional quality improvement projects, such as Centre care networking, individual quality improvement projects, group efforts and benchmarking are based on connecting patient data, registry data and individual efforts. There is also space for telehealth and patient-driven initiatives. Thus, quality improvement at the patient level is a central and decisive part of quality management in CF, accompanied by further and wider approaches at other levels.
2.3. Public reporting
Appropriate CF care and continuous improvement of clinical management are necessary to augment the well-being and quality of life of patients with CF  . Patient registries are of utmost importance not only from the experts' point of view but also from the patients' perspective. As well as providing reliable and comparable data in a given country, they also represent a valuable tool to lobby appropriate CF care. Registry data should be made available to patients and national health authorities  . In many European countries, CF – a rare disease – competes for adequate share of the national health budget. It is important, however, that the data are presented in a patient-friendly way  , and that patient representatives are trained in interpreting them.
In the USA, patient outcomes of each CF Centre have been laid open since 2006 ( www.cff.org//CCNP/CareCenterSelector/Index.cfm ). Interestingly, this effort did not lead patients to move to better performing Centres in any meaningful numbers.
2.4. Quality of life assessment
Over the past 20 years, a number of instruments have been developed to measure patient health status and to assess how patients feel or function with regard to their health conditions  . The questionnaires that measure quality of life in patients with CF (the revised CF questionnaire [CFQ-R] and the Cystic Fibrosis Quality of Life (CFQoL) questionnaire) are considered valid instruments with demonstrated reliability, internal validity, and sensitivity. As pulmonary exacerbations are clearly associated with worse symptoms of lung infection and health perception, these questionnaires represent an important tool to be used with clinical questions and national and international surveys, among other endpoints (clinical efficacy measures, surrogate endpoints or biomarkers)  . The European Medicines Agency recommends that in addition to demonstration of efficacy of treatment, a demonstration of benefit on health-related quality of life should be performed in CF trials  .
2.5. Patient satisfaction assessment
‘Patients feel confident when looked after by medical personnel who are experienced in the care of their condition’  . Therefore, quality improvement measures that start from patient satisfaction are under development in several countries. In Germany a nationwide study was conducted that examined patients' experiences and satisfaction with the care provided at their Centres  . The response rate of 71–74% is a reflection of how interested patients are in contributing to improvements in the quality of their care.
However, quality improvement measures focusing on patient satisfaction are only useful if the results are discussed between CF teams and patient representatives. A way to organize such an ongoing and continuous reflection is to establish discussion groups that meet regularly. Such discussion groups may also offer a straightforward tool to improve care management in those countries where quality assessment and improvement measures on a national level are just about to start. Discussion groups do require a lot of good will on the part of the caregivers, as well as training of the patient representatives involved.
A summary of the elements of patient-centred quality management is shown in Table 1 .
Questions and Answers
- Q1 What is the contribution of electronic patient files and follow-up charts in quality management in CF care?
- A1 Electronic patient files and follow-up charts are a basis for sharing data with patients, for individual comparison, Centre charts and for definition of therapy goals.
- Q2 How can appropriate respiratory and nutritional measures be installed and controlled individually in CF care?
- A2 By following national and international standards and definitions and using defined normal values in different age cohorts, best practice can be marked and individual aims can be set and managed.
- Q3 What is the contribution of patient-reported quality of life data and patient satisfaction questionnaires in quality improvement work?
- A3 Patient-reported quality of life data are an important subjective adjunct to description of quality at satisfaction and compliance level. Patient satisfaction questionnaires are opening up an additional dimension of interaction between patient and CF Centre in quality improvement.
Practical points and tools
- Electronic patient documentation
- Patient follow-up charts
- CF team sessions, discussion of single patients
- Setting quality goals
- Patient and Centre checklists
- Adherence to guidelines
- Planned intervention
- Education and training of physicians, families and patients
CF, cystic fibrosis.
3. Quality management at the Centre level
3.1. Centre care, certification and peer review
CF Centre care and the use of national and international patient registries have become essential features of healthcare and information exchange in the field of CF in many countries. Since 1995, the German CFQA project has collected demographic data and outcome parameters and the registry has evolved from a standard registry into an instrument of quality management. The German CFQA project also serves as the backbone in supporting quality assurance groups and as a benchmark project  . Quality management is now a major tool in CF Centres and is maintained by national registries. The analysis of registry data could lead to the certification of CF Centres as well as to the guided planning of structures and strategies in CF care. It could also serve as a basis for political action in the healthcare system and for improvements in quality awareness at all levels (individual, Centres, quality groups, political, charity institutions)  .
The CF Trust peer-review programme assesses services against national standards of care, identifies shortfalls and helps CF services to improve the care they provide. A revised programme for 2012 will result in peer-review reports being made available to the public for the first time, providing comprehensive, independently verified information about the performance of individual CF services  .
It is now recommended that CF patients should be cared for by a multidisciplinary team of specialist doctors, nurses and allied health professionals at a recognized specialist CF Centre.
3.2. Models of care, consensus documents
Different models of care have been outlined. The definition of the CF Centre, number of patients treated at the Centre (both lower and upper limit) as well as the number and expertise of staff members are given by different national and international consensus documents, including the Centre Framework paper in this supplement , , and .
Questions and Answers
- Q1 Do we have a nationwide definition of the specialist CF Centre? Can we agree on patient numbers and required staffing levels at CF Centres?
- A1 The level of expertise required to treat the complex multisystem symptoms and complications of CF can only be acquired by a multidisciplinary team of trained, experienced, specialist health professionals who routinely see a critical mass of patients at a specialist CF Centre.
- Q2 Do we have an agreement about key markers for evaluation of performance of specialist Centres?
- A2 The following are examples of key markers used in many countries:
- i microbiology, rate of new and chronic infections, lung function data, age groups
- ii nutritional data (body mass index percentile, body mass index, age groups).
- Q3 How can data collection and public reporting of care Centre data be a part of the quality improvement initiative?
- A3 By sharing data, the partnership between patients and caregivers can be strengthened. The analysis of data and establishment of national peer-review programmes could be used for the certification of individual CF Centres. It could also serve as a basis for political action in the healthcare system and for improvements in quality awareness at all levels.
4. Quality management at the regional and national level
The fundamental requirements for a functional and effective healthcare system is for all parties – patients, families, payers, healthcare professionals, healthcare system leaders and communities – to produce better outcomes for patients, better professional development and better performance for the healthcare organizations  . Quality and safety are the consequence of the functional interaction between healthcare providers and patients at the microsystem level, but physical resources, adequacy of funding and health policies influence both.
4.1. Health policies
Public health policies at the macrosystem level (either national or regional levels, depending on the country) include: 1) quality accreditation of care organizations, based on professional practice evaluation; 2) risk management, for instance to decrease iatrogenic disease and improve hygiene precautions; 3) professional development through continuous training and rewards.
Private policies, such as those developed by pharmaceutical companies or patient and family foundation initiatives, may complement or interfere with national public health policies. National or regional health policies and private initiatives need to converge into consistent incentives to sustain the engagement of professionals in continuous quality improvement over time. An example of this is the link between newborn screening and subsequent Centre care of the newly identified patients based on consensus  .
From the European public health policy perspective CF is classified as “rare disease” (i.e. occurring with the prevalence lower than 5 in 10,000 individuals) according to the “Regulation (EC) No 141/2000 of the European Parliament and of the Council from of 16 December 1999 on orphan medicinal products”. In this regard CF Centres should be in compliance with the European Union Committee of Rare Disease Experts guidelines for “Centres of Expertise for rare diseases” so that these could cooperate within the frame of European Reference Networks for Rare Diseases. This macrosystem measure is important since rare diseases (hence CF) have received a special status in Articles 54–55 of the European “Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the application of patients' rights in cross-border healthcare”. Such special status is potentially very important for CF centres located within the European Union in terms of reimbursement of CF care for patients originating from another Member State, including provision of transnational sharing of expertise, exchange of staff and eventually also of CF patients in selected instances (e.g. in those cases who could benefit from highly specialized care in a better resourced centre, or when local conditions would be temporarily unfavourable, or for patients from less favoured regions of the European Union). Finally, the rare diseases status also facilitates development and registration of orphan medicinal products (e.g. CFTR modulating therapies) by the industry and the European Medicines Agency, respectively.
4.2. Strategies of quality management at the national level
As the EuroCareCF analysis of demographic data from 35 countries shows, there is no single approach or strategy that works in all situations. However, there are principles that can help to develop a strategy suited to the situation in a particular region  . A strategy is a process, a way of agreeing what is to be done and by whom, and of ensuring that quality work is carried forward  . Strategies and experiences in several European countries are listed in Table 2 .
Country Quality management strategies Principles — initiatives France LLC and best practice Continuous professional development Germany Benchmarking and best practice, Centre certification Quality of patient outcomes Italy Peer reviews and accreditation Patient and family involvement as peers UK Peer reviews and LLC (site visits) Quality of patient outcomes and processes (adherence to guidelines)
LLC, learning and leadership collaborative.
4.3. Quality improvement learning collaboratives and learning and leadership collectives
Learning and leadership collectives (LLC) involve several care Centres in a yearly quality improvement programme. The programmes are based on the Dartmouth Institute Clinical Microsystem Approach (an action guide for accelerating the rate of quality improvement in CF care), and involve the training and coaching of the multidisciplinary care teams through four phases
- preparation phase
- 5P analysis (i.e. product, price, programme, process, people) and assessment of the Centre
- action phase, and
- transition phase.
Health systems in the USA, Germany, Sweden, the UK and France pursue quality improvement through learning strategies. Clinical outcomes attributed to quality improvement learning collaborative (QILC) include: identification and adoption of systematically studied evidence-based practices, decreased neonatal infection rates, cost-conscious prescriptive practices, improved patient safety, decreased emergency department waiting times and improved management of persons with chronic illness , , and .
Key factors associated with successful collaboration for quality improvement include availability of resources to support changes, multidisciplinary involvement, agreed aims and agenda, project ownership among members, and the essential role of leadership. These conditions depend on personal contact between participants, wide networking, mutual respect among all parties, accessibility of data and information sharing. Diversity among members strengthens the collaborative by contributing a range of perspectives  .
The CFF (USA) has developed LLCs  . The Dartmouth Institute Clinical Microsystems approach was used as the framework to improve the quality of CF care in the USA. Modelling on the US-CFF quality improvement initiative, a pilot QILC was initiated in France in 2011 and demonstrated that the US approach including national coordination and coaching is appropriate  with a few adjustments, namely the need for a part-time member of staff in each Centre whose role is one of a local coach, working closely with the physician leader of the CF Team.
An external evaluation highlighted the existence of obstacles, such as limited time and resources, staff and organizational changes, and lack of accurate and up-to-date information to measure outcomes  and . These shortcomings were positively balanced by success factors, mainly motivation of the CF team, a culture of patient-centred care, patient and parent involvement, physician leadership and clear agreed goals.
4.4. Ranking and learning from best practice (benchmarking)
Benchmarking involves the identification of healthcare programmes associated with the most favourable outcomes as a means to identify and spread effective strategies for care delivery  and . Variation in processes and outcomes suggests differences in the efficiency of delivery of care, and offers the opportunity to gain knowledge of the level of success that may be obtained with currently available therapies.
Quality benchmarks in CF use key nutritional and respiratory assessments such as body mass index (BMI), FEV1%, bacterial status and complications. Patient registries include annual data derived from the data collected at each visit to the CF Centres. Where well-established patient registries exist with high-quality data, ranking of the Centres offers the opportunity to identify potential best practice for treating patients with CF.
The next step is to attempt to determine how their excellence was achieved  and . The US CFF supported a benchmarking programme that used registry data to identify clinically excellent CF Centres and then to study their structural and cultural organizational features in addition to the specific practices that contribute to their outcomes. The underlying principle is that the practices and/or characteristics identified at high-performing Centres are drivers (and not just markers) of outcomes, which can be translated and applied to other Centres that are not performing so well.
A number of pitfalls complicate attempts to ascertain best practice  . Attention has to be paid to biases between Centres due to case mix. For example, Centres following patients with proportionately milder mutations may have better indicators than Centres following more severe patients (e.g. those registered on a transplantation list). Centres with small numbers of patients may present great variation in their indicators depending on the health status of just a few patients. Adult care Centres are fed by paediatric programmes, which determine the baseline disease status as well as the education of patients. Socioeconomic factors affect the population of patients in some Centres according to their location. It is important to consider case-mix adjustment to control for disproportionate distributions of sociodemographic and disease-specific risk factors at some programmes and locations, even if this may introduce new bias into the comparison.
Beyond the registry data, several key themes emerged from the benchmarking work: 1) the presence of a well-functioning care team working with a well-thought-out systematic approach to providing consistent care; 2) high expectations for outcomes among providers and families; 3) early and aggressive management, avoiding reliance on rescue therapies; 4) patients/families who are engaged, empowered and well informed on disease management and its rationale  .
The most frequently used criteria for benchmarking and peer review are as follows:
- physician leadership
- multidisciplinary care team
- access to care
- infection control
- sweat test quality
- follow-up care guidelines
- patient and family satisfaction survey.
CF care at the national/regional level has to adapt international guidelines (USA and Europe) to the local context. Adaptation means translation into the local language, adaptation to the context of the organization of care, dissemination through the Centres, and assessment of their implementation in the CF Centres. A successful experience  of appropriating international guidelines is illustrated by Cincinnati Children's Hospital, which set up a framework for adherence to prescribing guidelines in an outpatient setting, educating clinicians and sharing goals with families.
4.6. Peer review and quality accreditation programmes
Peer-review programmes enlist professionals to monitor the quality of patient care provided by their colleagues, in order to identify opportunities to improve the quality of patient care. They are designed to monitor the quality of the healthcare services offered to patients, to identify opportunities to improve patient outcomes, and to identify and prevent malpractice  .
In the EU there are different quality improvement accreditation programmes involving the peer-review method. The activity of preparing and undergoing accreditation has been shown to promote change in health organizations. It is important to:
- assure a minimum standard of care in every Centre; the standard must be set at the maximum achievable level, in the national/regional context, in order to stimulate improvement over the time;
- foster exemplary care, encouraging and supporting care Centre development;
- support new Centres in starting their activity;
- improve clinical outcomes.
At the national/regional level, a key recommendation is that a multidisciplinary committee, including patient and family representatives, should be established in order to start and develop programmes of peer-review accreditation according to published European standards. These programmes should be adapted to local needs and resources, to stimulate CF Centre improvement over time. Table 2 shows examples of national peer-review programmes.
4.7. Information systems at the national/regional level
According to the World Health Organization  , information systems need to apply consistently across the whole quality improvement programme so that comparisons in outcomes and progress can be made between parts of the programme. These information systems also need to be transparent, so that the widest possible range of stakeholders has access to the same information. The scope of the information includes: the availability to healthcare workers of information about best practice; the way in which the information is given to service users by those providing care; and the access by communities and individuals to information that will help them manage their own health. Any of these areas might require change as part of a strategy for quality improvement  .
In the course of a yearly collaborative quality improvement programme, key indicators and their current value are shared with the Centres involved, patients and families. This fosters harmonization and quality control of the data in the Centres. Results must be interpreted carefully and scientific measures should be applied to identify trends and factors of variability for the accurate monitoring of quality improvement work  .
4.8.1. PDSA cycles
Quality management is carried out using PDSA cycles, leading from a quality improvement plan (plan), to measuring appropriately and surveying quality indicators to changes in practice (do), to finding out about best practice (study), and finally, to induce new quality-improvement steps that will meet standards and guidelines and approach quality goals (act).
The results of quality improvement initiatives are not reported in the same way as traditional clinical research. Quality improvement reports tend to address ‘messier’ problems, involve more complex interventions, and require far greater attention to context. The ‘messiness’ of problems in quality improvement is a reflection of the real-life setting and the focus on routine care rather the controlled environment of a clinical trial. For example, an improvement project might ask: can patient outcomes be improved by changing the referral and appointment system to ensure timely access and better coordination between specialist and primary care services?  .
To drive improvement efforts, an annual report of patient outcomes, based on one value derived from the different measurements of the year and issued several months after the end of the period is not appropriate. Actual data that are updated at each visit and displayed on graphs incorporating the evolution in processes, delivery of care and patient outcomes are essential to provide feedback on the implementation of treatment/service improvements plans. This requires a CF information system to collect patient data regularly and to track the care delivered at each visit, and database management that issues reports for the team on weekly, monthly and quarterly bases.
Standardization, completion and quality control of the data collected at the Centres are essential to the relevance of the measure. Part of the improvement shown by the indicator comes from a higher quality of data collected. BMI or FEV1% are significantly dependent on the conditions of measurement (e.g. before or after a meal, related to the scale used, before or after physiotherapy).
Over the past 20 years, the concept of improvement of healthcare systems has moved away from top-down control, compliance and punishment towards bottom-up development, self-regulation and incentives. Quality measurement has shifted from resource inputs to performance outputs. Emphasis has moved from quality control and assessment to the definition of agreed and valid standards, systematic and reliable measurement of performance, implementation of action for change, repeated measurement and continuous improvement in a cycle or upward-moving spiral  . Thus, the new quality improvement tools of benchmarking, learning from best practice, PDSA cycles, LLC and accreditation are more adequate to accomplish quality improvement in CF. These methods are summarized in Table 3 .
- Delineate healthcare process
- Collect data over time to document variation in care practices and clinical outcomes
- Document unwanted and unnecessary variation
- Collect information regarding customer/beneficiary knowledge (e.g. measurements of illness burden, functional status, quality of life; recipients' assessment of the quality of their care)
- Adopt widespread public sharing of information
- Improve communication by building teams and enhancing group learning using specific skills (e.g. situation, background, assessment and request [SBAR])
- Create a leadership plan acknowledging: leading, following and making changes in healthcare
- Build knowledge (locally useful) then take initiative and use adaptive action, reviewing and reflecting
- Make small tests of change (e.g. Plan–Do–Study–Act cycles)
5. Quality management at the national level
5.1. Quality improvement
Not uncommonly, practitioners in a specific clinical setting will fail to prescribe recommended treatments; the reasons for under-utilization of recommended efficacious therapies are often site specific and relate to structural or educational barriers. Through an iterative process of quality improvement, one can begin to identify and intervene on the barriers to effect change in care.
5.2. Registries in quality improvement
In order to begin work in quality improvement, one needs to have a measure of the scope of the clinical problem. One of the key components of quality improvement is access to high-quality data regarding patient characteristics, treatments and clinical outcomes. Such data sources have historically been patient registries. Registries permit investigators and stakeholders to document variation in care where variation would not be anticipated. CF is ideally suited for evaluation of quality improvement research because of the existence in many countries of comprehensive patient registries. Some of the very early patient registries in CF were set up  and  to establish a more unified understanding of CF and to measure quality improvement. In 1966, the CFF Patient Registry (CFFPR) was started for this purpose and now contains detailed data on more than 26,000 individuals with CF  . The CFFPR has been used to evaluate survival and temporal changes in survival  , predictors of survival  , impact of sputum microbiology  and complications related to CF  . Similar advances have come from other registries (e.g. the UK CF Registry) identifying use of gentamicin as a particular risk factor for renal failure in CF  and highlighting the relationship between diabetes control and survival  . More recent publications from the USA have addressed process of care and access to care, which are key topics in quality improvement  and . Johnson et al. evaluated US CF Centres, ranking these Centres based on the median FEV1 within each of three age groups (6–12 years, 13–17 years and ≥ 18 years). They found that those Centres that saw their patients more frequently, with attendant lung function tests, sputum microbiology and more antibiotic use, consistently ranked higher  . These investigations can then lead to the design of interventions that improve care practice and patient-centred high-value outcomes.
5.3. Guidelines in CF for quality improvement purposes
One of the key elements of quality improvement is a clear understanding of what constitutes appropriate and high-quality care. One of the goals of quality improvement is to ensure that recommended treatments are indeed offered and utilized by patients in whom the treatments have demonstrated efficacy. Guideline documents have been published to help the CF community evaluate the existing evidence and establish standards of care (e.g. care of the infant and treatment of lung infections)  and . These documents provide a systematic approach to evaluating the literature and a set of recommendations that can then be integrated into benchmarking. Such documents represent the standards for current care in CF, creating a roadmap to continued success in the management of this disease. One of the key challenges of guidelines is that they can differ in their recommendations. These differences may be due to differences in healthcare systems, interpretation of data, and interpretation of risks and benefits of interventions. Guidelines are clearly fluid and will change over time as more information is gathered regarding approaches to CF care.
5.4. Nationwide benchmarking in CF for quality improvement purposes
In many countries patient advocacy groups have set goals to improve the survival and outcome of individuals with CF. These groups represent the earliest phase of quality improvement in CF. As a result of these efforts, quality of care for people with CF has improved significantly, with an associated improved survival  . Development of patient registries has been the engine behind this success. Although improving survival is a key goal in quality improvement and benchmarking, other important metrics should also be tracked. There have been several key advances in this area over the past decade. German CF Centres have made quality improvement a major focus in their CF care  and . This project was able to demonstrate first the temporal improvements in outcome and then improvements in care but importantly, it demonstrated variation in care practices among the 93 Centres in Germany. The project then developed benchmarking indicators and a PDSA cycle  . As results from this work translate into change in care practice, continued improvement in CF outcomes will be realized  . In another example, in 2006 in a move toward benchmarking, the US CFF made Centre-specific performance indicators transparent to the public, promoting this action as an initiative to ‘accelerate the rate of improvement’ through benchmarking. Top-performing Centres were used as models of best practice with the hope of disseminating successful processes to other Centres, and thus reducing national variability in practice patterns and outcomes. The US CFF also launched a series of action-oriented training programmes (LLCs) to increase the capacity for quality improvement across the CF clinical care network  . Each Centre participating in one of the LLCs performed a quality improvement project over the course of a year. Examples included a project to standardize pulmonary exacerbation care  and benchmarking to improve the screening rates for CF-related diabetes  .
5.5. Role of quality improvement in newborn screening
Newborn screening provides a unique opportunity for quality improvement in CF. Identifying individuals at birth provides several windows of opportunities to intervene early in the disease. Such interventions could lead to the prevention of structural lung disease occurring prior to clinical symptomatology in CF babies  . Newborn screening allows CF providers and researchers to more formally understand the early events that lead to later clinical disease  and evaluate the role of earlier interventions  . Recent work made possible by newborn screening was employed to establish a definition of exacerbation in very young children  . Understanding best practices, how to benchmark care, and how best to track children with CF identified by newborn screening will be essential to further advance the care of these patients. Guidelines and standards of care are now available for the management of this particular CF population and will remain essential  . National data registries will need to change accordingly to track clinical interventions and outcomes. A key challenge remaining relates to the limited data for treatments early in disease and the challenges to establish treatments in this patient population. In addition from a larger perspective, newborn screening poses new challenges and opportunities to ensure early and timely access to care for persons with CF and potentially access to new promising therapies for eligible patients.
Challenges will also remain given the differences in algorithms for newborn screening. All screening tests involve trade-offs between sensitivity and specificity. Marked differences have been noted in positive predictive value depending on the approach taken  and . One of the key issues with regard to choosing different protocols for newborn screening will be the identification of carriers and understanding the natural history of the rarer genotypes identified through newborn screening. Integration of data from newborn screening into patient registries will help to clarify some of the key issues that arise from screening.
Questions and answers
- Q1 How does one ensure that high-quality accurate data are recorded in registries?
- A1 One could consider doing random on-site audits in addition to electronic data audits.
- Q2 Should patient registries go through routine validation steps given the role they have in measuring and assessing quality of care?
- A2 Validation could include data audits but also validation of data steps involved in generated specific high-value outcome measures (e.g. FEV1% predicted).
- Q3 How can registries achieve standardized definitions of data elements and standardized reporting to ensure improved comparisons when performing comparisons between countries?
- A3 This could be achieved by creating an international working group on registry standardization.
- Q4 How can registries reduce the time from data entry to feedback of results to Centres and patients?
- A4 One solution could entail real-time data entry.
- Q5 What are the essential data elements related to newborn screening that need to be collected in registries to establish appropriate quality measures in the future?
- A5 Potential variables include age of screening, approach taken for screening and results of screening
- Q6 How do countries address variable newborn screening protocols within their borders?
- A6 This could be addressed by having a clear outline of all approaches to newborn screening and to have a data element that clearly lists the approach taken for each individual.
- Q7 How should patient registries be employed to formally evaluate newborn screening protocols?
- A7 One strategy would be to compare the introduction of newborn screening with interrupted time series analysis in nations, provinces or states with differing times of introduction of these protocols.
6. Quality management at the international level
“More radically, I would suggest that we don't need international comparisons. Rather, what we need is international learning.” K. Walshe (2003)  .
6.1. International comparisons: state of the art
Comparisons of quality management practices across countries pose the same problems as comparisons within the same country, but add the complexity of differences in healthcare systems and data collection practices. Dreachslin et al.  identified the main obstacles to international data quality comparisons as a lack of a uniform clinical database, common definitions and data collection practices.
6.1.1. Choice of indicators and their definition
The choice of indicators is crucial when quality management comparisons are carried out on patients' health status and on healthcare systems. Various indicators have been suggested and it is therefore important to consider the validity and necessity of measures, as defined by Kerr  and . Diagnosis, healthcare services, and the outcomes of morbidity and mortality are suggested indicators  . However, quality assessment and improvement also require expert judgement and therefore quality indicators are not the panacea; learning through the sharing of experiences and networking is also important  . There is also a risk that a focus on indicators in certain areas will exclude consideration of other equally important areas and that long term outcomes may not be included  .
The transferability of quality indicators for healthcare systems across countries is feasible, but most often it is subject to adaptation according to the specific context of the different countries  . Particular attention should be paid to the level of detail in the definition of international indicators of quality management. In an attempt to have uniformity across countries there is a risk that indicators will become uninformative and result in the collection of information that is too generic  . Similarly, some indicators might reflect only local needs, and are therefore unsuitable for international comparison  .
Uniformity should be present for inclusion and exclusion criteria: potential selection bias in patient registration and information recording might affect the outcome of comparisons. It is therefore advisable to investigate whether inclusion/exclusion criteria or different processes of registration might be responsible for any differences found. To avoid the biases that might be introduced by case-mix in outcome measures, the recording of ‘near misses’ could be used instead  .
Finally, data collection procedures and data quality should be part of the quality management process. In fact, data quality is an essential aspect of research, and one must remember the old adage ‘garbage in, garbage out’. At the national level, the reduction of missing data eased the comparison and improved the follow-up in one study  . For this reason, data auditing processes are advised  .
6.1.2. PDSA cycles
It is well recognized that reporting of differences would be a useless ranking exercise if not followed by a change in behaviour/practices  . It is important to define a strategy for identifying differences between countries, exploring why these differences exist and building what Stern et al. called a learning process and quality improvement procedure  .
It is evident, though, that such a process is rather complicated in international settings, where different factors might lead to different outcomes and therefore confounding effects might lead to different outcomes or different quality indicators. Clearly, data analysis has a fundamental role: comparisons can be carried out in a mere descriptive way by means of summary tables and comparative graphs. However, a deeper understanding of the differences between countries should be carried out after also adjusting for potential confounders. Moreover, after factors responsible for different quality management levels have been identified, discussion on the appropriateness of transferring practices across countries are necessary, as what works in one country might not work in another, or it might simply not be transferable  .
Finally, some authors advocate the need for a governance body that oversees the data quality improvement process and sets up the appropriate measuring criteria, data collection procedures, data analyses methods, and rewarding schemes  and .
6.2. International comparisons: a consensus
In order to set up an international quality improvement process, agreement at the international level must be reached on the following aspects: choice of indicators of quality monitoring, choice of most suitable repository to store such indicators, data analysis approaches (such as acknowledgement of selection bias and confounding factors), implementation of PDSA cycles and governance of quality management process. The following sections outline the consensus reached for each of these aspects, and suggestions are made for areas in need of work.
6.2.1. Choice of indicators
Comparisons on the following areas of quality management should be carried out internationally: healthcare services, outcomes and data quality.
126.96.36.199. Healthcare services
Indicators for evaluation of healthcare services have been proposed and used in the medical literature, but in CF their use has not been well documented, especially in international settings.
In the previous consensus statement on the standards of care for CF, Kerem et al.  identified key services, facilities and personnel to be adopted by specialized CF Centres, recommended routines of CF care for outpatient, inpatient, shared and transitional care, and recommended follow-up tests to be carried out at annual assessment. These standards of care have paved the way for the definition of indicators for international comparison, in particular for the area of healthcare services. Table 4 lists candidate indicators derived from the recommendations updated in the present standards of care paper (see Section 3 , Quality management at the Centre level)  .
Area Proposed indicator CF Centre definition Funding of CF Centre guaranteed by the provider of medical care
Number of patients followed
Establishment of links with consultants with expertise in the fields recommended in the standards of care consensus
Presence of referral and assessment protocol with a transplant Centre
Availability of a radiology department with CT scanning facilities
Availability of a pulmonary function laboratory
Availability of a microbiology service with established contacts with a CF microbiology reference laboratory
Availability of diagnostic capability including sweat testing and CFTR gene mutation analysis
Availability of guidelines for the treatment of CF complications
24-hour access to the CF Centre for telephone advice, emergencies or consultations
Members of the team Presence of CF Centre Director
Presence of CF Consultant
Presence of CF Clinical Nurse Specialist
Presence of CF Physiotherapist
Presence of CF Dietitian/Nutritionist,
Presence of CF Social Worker
Presence of CF Psychologist
Presence of CF Clinical Pharmacist
Presence of CF Clinical Microbiologist
Presence of consultant, registrar, staff grade specialist nurse, physiotherapist, dietitian, social worker, psychologist, secretary, pharmacist for the full-time equivalent 
Outpatient care Frequency of visits
Place of visit
Presence of CF physician and nurse at every visit
Accessibility of all members of the team at every visit
Execution of recommended routine tests, as appropriate for the age of the patient
Revision of treatment and medications
Implementation of segregation policy according to patient microbial status
Admission or home intravenous treatments within 24–48 h
Inpatient care Number of beds to allow immediate admission
Presence of infection control policy
Availability of single rooms with en-suite toilet and bathroom
Availability of hand-washing facilities
Availability of concomitant review by allied health professionals
Assessment of hyperglycaemia and overnight oxygen saturation at each admission for infective exacerbation
Regular sputum microbiology
Regular spirometry measurement
Physiotherapy (including sputum mobilization techniques), twice daily
Availability of facilities for supervised physical exercise
Availability of protocols for dosing and administration of antibiotics, treatment of a pneumothorax, management ofhaemoptysis, diagnosis and treatment of ABPA and CF-related diabetes
Weekly discussions in the multidisciplinary meeting of inpatients and those receiving intravenous antibiotic therapy
Shared care Number of patients followed in the satellite CF unit
Presence of input in the satellite CF unit from: dietitian, physiotherapist and nurse, each with a special interest in CF
Presence of CF-dedicated clinics in the CF satellite unit
Periodic contact (once/twice a year) between CF care and satellite CF unit annual assessment performed by the CF Centre
Transitional care Availability of a system to allow transition from paediatric to adult care
Presence of continuity of diagnostic and treatment protocols
Agreement between transition Centres on infection control policies
Review of children and parents before the handover of care
Introduction to the new Centre before transition takes place
Presentation of differences between the transition Centres performed before transition
Written report on the patient by all disciplines attached to paediatric care
Welcome of the patient on first day of transition to the new Centre
Annual assessment History of all medical and life events since the previous annual review
Full clinical examination
Review by a CF specialist physiotherapist
Spirometry in patients over 5 years of age
Nutritional review by a CF specialist dietitian
Time with social worker and/or psychologist if required
Blood tests, sampling for faecal pancreatic elastase, faecal fat, chest X-ray, liver ultrasound, sputum or swab as indicated in the ‘Standards of care’ paper
Oral glucose tolerance test as indicated in the ‘Standards of care’ paper]
Surveillance of bone mineral density
Repetition of sweat test for patients new to the Centre
Identification of genotype, if not already done, for patients new to the Centre
Confirmation of pancreatic insufficiency for patients new to the Centre
Introduction of the Centre to patients new to the Centre
Lung function tests Spirometry at every visit (FVC, FEV1, FEFmax, FEF25–75)
Pulmonary function tests other than spirometry when clinically indicated
Execution of tests in a large ventilated room, using methods to reduce cross infection
Segregation of patients according to their microbial status
New diagnoses Ability to visit the patient within 24 h from diagnosis
Implementation of initial assessment specifications
Initiation of educational programme
Initiation of treatment programme
Diagnosis in adulthood
Availability of tests indicated in the ‘Standards of care’ paper
ABPA, allergic bronchopulmonary aspergillosis; CF, cystic fibrosis; CT, computed tomography; FEF, forced expiratory flow; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity.
ECFS encourages the creation of an international working group, composed of experts in evaluation of healthcare systems, CF specialists and data managers of CF databases, with the aim of evaluating whether these candidate indicators have the required characteristic for international comparisons. In particular, evaluation of the proposed indicators should concentrate on the following aspects:
- Do such indicators have the desired characteristics: validity, necessity, transferability?
- Do such indicators have an adequate level of detail? Are they informative or are they too vague? Do they reflect only local needs?
- Is there a risk of tunnel vision with the choice of such indicators?
- Are long-term indicators available and usable?
188.8.131.52. Health outcomes
In the CF literature, comparisons of health outcomes have been carried out nationally , , , and  and internationally , , , , , , , , , , and . Comparisons have been performed mainly for survival, lung function and nutrition. Median age at death, median predicted survival, FEV1, forced vital capacity, occurrence of lung infections, weight, height and BMI have been used as indicators for comparisons.
All these indicators have desirable characteristics: there is a large consensus in the scientific CF community on their ability to reflect the patient's health status; they are routinely recorded in the clinical notes because they are used for the clinical management of the patient; they have an adequate level of detail to express the patient's health status; they do not reflect only local needs; they focus on various aspects of CF; and some of them take into account long-term outcomes. The main problems with the use of such indicators have been in terms of transferability: international comparisons through their use have proven difficult due to different timings of measurements (e.g. recording of best vs. last FEV1 of the year), dissimilar definitions (e.g. chronicity of infections)  , different detection rates (e.g. genotyping) or frequency of sampling (e.g. microbiological testing)  and , potential patient selection bias , , and , amount of missing data  .
ECFS urges the international CF community to come to an agreement on core aspects of CF health outcomes, and report national-level indicators on such aspects on a routine basis, primarily through national CF registries. A proposal on sharing such information was put forward in 2009  and a choice of Centre-level indicators was outlined. This proposal has been further developed and other indicators have been proposed  .
Another example of international comparison of health outcomes and health processes (e.g. diagnostic practices) is given in the annual data report of the European Cystic Fibrosis Society Patient Registry  and . Table 5 summarizes the indicators on health outcomes and health processes that should be considered and improved for international comparison purposes  and .
Area Indicator Stratification Limits Outcome Median age By sex Proportion of patients aged 18 years or more Median FEV1% predicted By sex and age Patients aged 6 + years Median BMI percentile By sex and age Number of deaths in current year By sex Median age at death (deaths in current year) By sex Mean BMI By sex and age Patients aged 18 + years Mean BMI percentile By sex and age Patients aged 2–17 Mean FEV1% predicted By sex and age Patients aged 6 + years Mean, minimum, maximum, quartiles of age
Proportion of patients over 18 years
Proportion of patients deceased during current year
Mean and median age at death
Proportion of patients living with lung transplant
Proportion of patients living with liver transplant
Mean, minimum, maximum, quartiles of FEV1% predicted By age Patients without lung function FEV1% predicted groups (< 40/40–80/> 80%) By age Patients without lung function Prevalence of chronic infection by Pseudomonas aeruginosa
Prevalence of chronic infection by Burkholderia spp.
Prevalence of chronic infection by Staphylococcus aureus
Prevalence of infection by non-tuberculous mycobacteria
Prevalence of infection by Stenotrophomonas maltophilia
Mean, minimum, maximum, quartiles of Z-scores for height By age Mean, minimum, maximum, quartiles of Z-scores for weight By age Mean, minimum, maximum, quartiles of Z-scores for BMI By age Proportion of patients with BMI < 18.5 By age and sex Patients aged 18 + years Prevalence of allergic bronchopulmonary aspergillosis
Prevalence of pneumothorax
Prevalence of haemoptysis
Prevalence of malignancy
Prevalence of liver disease
Number of patients living with transplanted lung(s) By age and sex Number of patients living with transplanted liver By age and sex Number of deaths in current year By age and sex Age at death groups for deaths occurred in current year By sex Cause of death for deaths occurred in current year Processes Number of new diagnoses in current year Percentage of new cases diagnosed by newborn screening in current year
Median age at diagnosis
Median age at diagnosis for new diagnoses
F508del genotype (homozygote/heterozygote/other/not genotyped)
Mean, minimum, maximum, quartiles of age at diagnosis
Age at diagnosis groups
Proportion of patients who underwent neonatal screening Patients aged 5 + years Proportion of patients with DNA analysis
BMI, body mass index; FEV1, forced expiratory volume.
184.108.40.206. Data quality
Data quality should be part of an international quality monitoring process. Improvement of the level of accuracy of information recorded should be attained by motivation and proper training of the individuals in charge of data retrieval and data recording, by implementation of automatic systems for error detection, and by implementation of efficient procedures for error correction. Initiatives for sharing international learning and expertise on data quality control processes should be encouraged, such as the one initiated by the European Cystic Fibrosis Society Patient Registry  .
6.2.2. Data analysis and metadata sharing
Outcomes of international comparisons are particularly prone to differences that might be due to confounding factors and to differences in patient selection. These confounders should be accounted for in the data analysis phase. Statistical methods for confounding control and case-mix adjustment can be used, although their implementation might be difficult in such a complex context, but at least simpler methods such as stratification and subgroup analysis should be used whenever necessary. It is essential that potential sources of patient selection bias are carefully scrutinized so that fair comparisons are carried out across countries in groups of patients that are as homogeneous as possible.
Another fundamental aspect of data analysis is the disclosure of all important technical information that might affect results. Reference values used to compute standard deviation scores for anthropometric measurements, or equations used to compute percentage of predicted values for lung function tests, specification of inclusion/exclusion criteria are examples of technical information that should be specified.
6.2.3. Data collection and choice of repository
The previous sections have described the elements needed for international comparisons: choice of indicators for healthcare services, processes and outcomes, the implementation of data analysis methods accounting for confounding effect and selection bias, the sharing of knowledge on data quality, the sharing of technical information on data analyses. All these elements could be conveniently gathered in a unique repository, such as the one proposed by Sims  .
International agreement should be reached on the choice of such a repository, and on the choice of the kind of information to be stored, as well as the level of detail. Examples of information stored are: aggregated results of indicators chosen for international comparisons, documentation of methodology used for data collection and data analysis, material useful for the exchange of experiences with different initiatives for quality improvement.
6.2.4. Implementation of PDSA cycles and governance of quality management processes
For the quality monitoring process to be effective, the PDSA cycle should be appropriately implemented and an efficient governance system should be set up.
It is recommended that international agreement is reached on how the governance process should be organized and sustained. A defined group of dedicated people, with the ability to introduce changes and measure the impact of those changes, should be set up. If the indicators chosen for international comparisons are not present in the existing databases (e.g. patient registries, administrative databases, routine health statistics reports), national registries should be urged to collect such information and to create a specific repository to store aggregated information.
Stimulation of participation in quality monitoring programmes, promotion of networking and experience sharing for the learning process, and audit on indicators and on data collection procedures are among the tasks of this group.
6.2.5. Patient involvement in international comparisons
Patient involvement at each level of the quality monitoring process is fundamental: quality improvement is for the patients' benefit and their empowerment and contribution to the process are essential.
Active involvement of patients is successfully attained in many countries through the sharing of information in which technical jargon is avoided. The distribution of fact leaflets, patient-friendly versions of annual data reports, and web pages of CF registries dedicated to the patients are examples of how the CF and registry specialists have granted the patients access to information in a transparent and comprehensible way. Patients thus have the opportunity to be an active part of healthcare, and through their representatives in the governance bodies can influence the implementation of the changes necessary to improve quality.
Conflict of interest
C.H. Goss: Board membership, Transave Inc., no personal fees, and KaloBios Pharmaceuticals, fee donated to the author’s institution; grants from Transave Inc. and Vertex Pharmaceuticals; lecturer for F. Hoffmann-La Roche Ltd, Johns Hopkins University, and European Cystic Fibrosis Society; grant from Gilead Sciences for participation in review panel; grants to the author’s institution from Cystic Fibrosis Foundation, FDA and NIH; all outside the submitted work. L. Viviani: personal fees from Effetti s.r.l., outside the submitted work. J.S. Elborn: President of ECFS. Institutional payments for consultancy and clinical trials from Vertex, Gilead, Novartis, outside the submitted work. C. Castellani: consultancy for Vertex and Gilead, lectures for Chiesi and Novartis, outside the submitted work. M. Stern, D. Pougheon Bertrand, E. Bignamini, M. Corey, B. Dembski, T. Pressler, and G. Rault have no conflicts of interest to report.
The authors wish to acknowledge many fruitful discussions in the quality management team and help by Elaine Gunn, Milan Macek, Jo Osmond and Harm Tiddens.
-  P.A. DiSant'Agnese. Cystic fibrosis of the pancreas. Am J Med. 1956;21:406-422
-  H. Shwachman, L.L. Kulczycki. Long-term study of one hundred five patients with cystic fibrosis; studies made over a five- to fourteen-year period. AMA J Dis Child. 1958;96:6-15
-  C.F. Doershuk, L.W. Matthews, A.S. Tucker, H. Nudleman, G. Eddy, M. Wise, et al. A 5 year clinical evaluation of a therapeutic program for patients with cystic fibrosis. J Pediatr. 1964;65:677-693
-  W.J. Warwick, R.E. Pogue. The prognosis for children with cystic fibrosis based on reasoned approaches to therapy: past, present, and future. J Asthma Res. 1968;5:277-284
-  H. Shwachman, M. Kowalski, K.T. Khaw. Cystic fibrosis: a new outlook. 70 patients above 25 years of age. Medicine. 1977;56:129-149
-  D.N. Crozier. Cystic fibrosis: a not-so-fatal disease. Pediatr Clin North Am. 1974;21:935-950
-  D. Gurwitz, M. Corey, P.W. Francis, D. Crozier, H. Levison. Perspectives in cystic fibrosis. Pediatr Clin North Am. 1979;26:603-615
-  M. Corey, F.J. McLaughlin, M. Williams, H. Levison. A comparison of survival, growth, and pulmonary function in patients with cystic fibrosis in Boston and Toronto. J Clin Epidemiol. 1988;41:583-591
-  Cystic Fibrosis Foundation. Cystic Fibrosis Foundation Patient Registry 2011 annual data report. (, 2012) [Bethesda, Maryland]
-  Cystic Fibrosis Canada. Canadian Cystic Fibrosis Patient Data Registry report. 2010. (, 2011) [Toronto]
-  Cystic Fibrosis Foundation. http://www.cff.org/LivingWithCF/CareCenterNetwork/QualityImprovement/ (2013)
-  D. Salvatore, R. Buzzetti, E. Baldo, M.L. Furnari, V. Lucidi, D. Manunza, et al. An overview of international literature from cystic fibrosis registries. Part 4: update 2011. J Cyst Fibros. 2012;11:480-493
-  European cystic fibrosis society patient registry newsletter. http://www.ecfs.eu/projects/ecfspr/newsletters (January 2013) [Issue 3]
-  The ECFS Patient Registry annual data report. 2008–2009 data. version 03. https://www.ecfs.eu/files/webfm/webfiles/File/ecfs_registry/ECFSPR_Report0809_v32012.pdf (2012) Available from:
-  E. Kerem, L. Viviani, A. Zolin, S. Macneill, E. Hatziagorou, H. Ellemunter, et al. Factors associated with FEV1 decline in cystic fibrosis: analysis of the data of the ECFS Patient Registry. Eur Respir J. 2013;10.1183/09031936.00166412 [Epub ahead of print]
-  B. Wiedemann, G. Steinkamp, B. Sens, M. Stern. The German Cystic Fibrosis Quality Assurance Project: clinical features in children and adults. Eur Respir J Eur Respir J. 2001;17:1187-1194
-  H.H. Gutierrez, I. Sanchez, D.V. Schidlow. Cystic fibrosis care in Chile. Curr Opin Pulm Med. 2009;15:632-637
-  W.J. Morgan, S.M. Butler, C.A. Johnson, A.A. Colin, S.C. FitzSimmons, D.E. Geller, et al. Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicentre, observational study of patients with cystic fibrosis in the U.S. and Canada. Pediatr Pumonol. 1999;28:231-241
-  M.S. Schechter. Benchmarking to improve the quality of cystic fibrosis care. Curr Opin Pulm Med. 2012;18:596-601
-  M. Rosenfeld, J. Emerson, S. McNamara, K. Joubran, G. Retsch-Bogart, G.R. Graff, et al. Baseline characteristics and factors associated with nutritional and pulmonary status at enrollment in the cystic fibrosis EPIC observational cohort. Pediatr Pulmonol. 2010;45:934-944
-  C.A. Byrnes, S. Vidmar, J.L. Cheney, J.B. Carlin, D.S. Armstrong, P.J. Cooper, et al. Prospective evaluation of respiratory exacerbations in children with cystic fibrosis from newborn screening to 5 years of age. Thorax. 2013;68:643-651
-  B. Martin, M.S. Schechter, A. Jaffe, P. Cooper, S.C. Bell, S. Ranganathan. Comparison of the US and Australian cystic fibrosis registries: the impact of newborn screening. Pediatrics. 2012;129:48-55
-  Closing the quality gap: revisiting the state of the science series: quality improvement interventions to address health disparities. Review protocol (Agency for Healthcare Research and Quality, Rockville, MD, 2011) [ http://www.ahrq.gov/clinic/tp/gapdisptp.htm ]
-  D.M. Berwick. The science of improvement. JAMA. 2008;299:1182-1184
-  K.G. Shojania, J.M. Grimshaw. Evidence-based quality improvement: the state of the science. Health Aff (Millwood). 2005;24:138-150
-  D.M. Berwick. Continuous improvement as an ideal in health care. N Engl J Med. 1989;320:53-56
-  E.C. Nelson, M.M. Godfrey, P.B. Batalden, S.A. Berry, A.E. Bothe, K.E. McKinley, et al. Clinical microsystems, Part1: The building blocks of health systems. Jt Comm J Qual Patient Saf. 2008;34:367-378
-  M.S. Schechter, P. Margolis. Improving subspecialty healthcare: lessons from cystic fibrosis. J Pediatr. 2005;147:295-301
-  H.B. Quinton, G.T. O'Connor, for the Northern New England CV Cystic Fibrosis Consortium. Current issues in quality improvement in cystic fibrosis. Clin Chest Med. 2007;28:459-472
-  M. Stern, B. Wiedemann, P. Wenzlaff, on behalf of the German Cystic Fibrosis Quality Assessment group. From registry to quality management: the German Cystic Fibrosis Quality Assessment project 1995–2006. Eur Respir J. 2008;31:29-35
-  M. Stern. The use of a cystic fibrosis patient registry to assess outcomes and improve cystic fibrosis care in Germany. Curr Opin Pulm Med. 2011;17:477-573
-  H. Ellemunter, J. Eder, G. Steinkamp. Structured care in an ISO certified Centre for patients with cystic fibrosis and their families. Pneumologie. 2011;65:615-623
-  T.G. Liou, E.P. Elkin, D.J. Pasta, J.R. Jacobs, M.W. Konstan, W.J. Morgan, et al. Year-to-year changes in lung function in individuals with cystic fibrosis. J Cyst Fibros. 2010;9:250-256
-  D. Taylor-Robinson, M. Whitehead, F. Diderichsen, H. Vebert Olesen, T. Pressler, R.L. Smyth, et al. Understanding the natural progression in %FEV1 decline in patients with cystic fibrosis: a longitudinal study. Thorax. 2012;67:860-866
-  N. Pillarisetti, E. Williamson, B. Linnane, B. Skoric, C.F. Robertson, P. Robinson, et al. Infection, inflammation and lung function decline in infants with cystic fibrosis. Am J Respir Crit Care Med. 2011;184:75-81
-  N.C. Kraynack, J.T. McBride. Improving care at cystic fibrosis centers through quality improvement. Semin Respir Crit Care Med. 2009;30:547-558
-  E.T. Zemanick, J.K. Harris, S. Conway, M.W. Konstan, B. Marshall, A.L. Quittner, et al. Measuring and improving respiratory outcomes in cystic fibrosis lung disease: opportunities and challenges to therapy. J Cyst Fibros. 2010;9:1-16
-  T.A. Glauser, P.H. Nevins, J.C. Williamson, M. Abdolrasulnia, G.D. Salinas, J. Zhang, et al. Adherence to the 2007 cystic fibrosis pulmonary guidelines: a national survey of CF care centers. Pediatr Pulmonol. 2012;47:434-440
-  G.L. McPhail, J. Weiland, J.D. Acton, M. Ednick, A. Chima, R. VanDyke, et al. Improving evidence-based care in cystic fibrosis through quality improvement. Arch Pediatr Adolesc Med. 2010;164:957-960
-  V.A. Stallings, L.J. Stark, K.A. Robinson, A.P. Feranchak, H. Quinton. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc. 2008;108:832-839
-  I.E. Moen, K. Nilsson, A. Andersson, M.W. Fagerland, G. Fluge, A. Hollsing, et al. Dietary intake and nutritional status in a Scandinavian adult cystic fibrosis population compared with recommendations. Food Nutr Res. 2011;55:7561
-  A. Leonard, E. Davis, B.J. Rosenstein, P.L. Zeitlin, S.M. Paranjape, D. Peeler, et al. Description of a standardized nutrition classification plan and its relation to nutritional outcomes in children with cystic fibrosis. J Pediatr Psychol. 2010;35:6-13
-  L.J. Stark, L. Opipari-Arrigan, A.L. Quittner, J. Bean, S.W. Powers. The effects of an intensive behavior and nutrition intervention compared to standard of care on weight outcomes in CF. Pediatr Pulmonol. 2011;46:31-35
-  P.B. Davis. Cystic fibrosis since 1938. Am J Respir Crit Care Med. 2006;173:475-482
-  CF Europe. http://www.cf-europe.eu/
-  Cystic Fibrosis Foundation Patient Registry. 2011 Annual Data Report. (Cystic Fibrosis Foundation, Bethesda, Maryland, 2011) [ http://www.cff.org/research/ClinicalResearch/PatientRegistryReport ]
-  H.G. Goss, A.L. Quittner. Patient-reported outcomes in cystic fibrosis. Proc Am Thorac Soc. 2007;4:378-386
-  N. Mayer-Hamblett, B.W. Ramsey, A.K. Kronmal. Advancing outcome measures for the new era of drug development in cystic fibrosis. Proc Am Thorac Soc. 2007;4:370-377
-  European Medicines Agency. Committee for medicinal products for Human Use (CHMP). Guidelines on the Clinical Development of Medicinal Products for the Treatment of Cystic Fibrosis (, Oct. 22 2009) [London, http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/12/WC500017055.pdf ]
-  E. Kerem, S. Conway, S. Elborn, H. Heijerman, for the Consensus Committee. Standards of care for patients with cystic fibrosis: a European consensus. J Cyst Fibros. 2005;4(7–26):20
-  G. Steinkamp, C. Schwarz, K. Stahl, M.C.F. Busche. Care through the patient's eyes — a nationwide survey on patients' experience and satisfaction with services using a CF-specific questionnaire. Pediatr Pulmonol. 2012;47(S35):404 (abstract 492)
-  B.S. Quon, C.H. Goss. A story of success: continuous quality improvement in cystic fibrosis care in the USA. Thorax. 2011;66:1106-1108
-  http://www.cftrust.org.uk/aboutus/annualreview/CF_Trust_Annual_Review_2011_%28web%29.pdf
-  https://www.cysticfibrosis.org.uk/media/82070/CD_Standards_of_Care_Dec_11.pdf
-  http://www.cff.org/treatments/CFCareGuidelines/AgeSpecificCare/
-  P.B. Batalden, F. Davidoff. What is “quality improvement” and how can it transform healthcare?. Qual Saf Health Care. 2007;16:2-3
-  I. Sermet-Gaudelus, S.J. Mayell, K.W. Southern. Guidelines on the early management of infants diagnosed with cystic fibrosis following newborn screening. J Cyst Fibros. 2010;9:323-329
-  G. Mehta, M. Macek Jr., A. Mehta, European Registry Working Group. Cystic fibrosis across Europe: EuroCareCF analysis of demographic data from 35 countries. J Cyst Fibros. 2010;9(Suppl. 2):5-21
-  World Health Organization. Guidance on developing quality and safety strategies with a health system approach. (World Health Organization Regional Office for Europe, Copenhagen, 2008)
-  M. Stern, N. Niemann, B. Wiedemann, P. Wenzlaff, German CFQA Group. Benchmarking improves quality in cystic fibrosis care: a pilot project involving 12 Centres. Int J Qual Health Care. 2011;23:349-356
-  L.R. Ayers, S.C. Beyea, M.M. Godfrey, D.C. Harper, E.C. Nelson, P.B. Batalden. Quality improvement learning collaboratives. Qual Manag Health Care. 2005;14:234-247
-  G. Rault, D. Pougheon-Bertrand, L. Gueganton, G. Minguet, P. Lombrail. CF quality improvement program: a pilot phase to experiment the US QIP approach in France. Poster; ECFS Conference, Dublin, Ireland (, June 6–9 2012)
-  M.S. Schechter, A. Leonard, J. Nash, H. Quinton, K. Richards, K. Sabadosa, et al. Benchmarking: signature themes. Pediatr Pulmonol. 2006;(Suppl. 29):122-123
-  R.G. Homchick, L.R. Hayward. Chapter 16. Peer review and quality assurance requirements. D.W. Tremaine, JD Organization (Eds.) 3rd ed. (Washington Health Law Manual, 2009)
-  World Health Organization. Quality of care: a process for making strategic choices in health systems. (World Health Organization, Geneva, 2006)
-  E.C. Nelson, P.B. Batalden, M. Godfrey. Measurement and monitoring. Quality by design: a clinical microsystems approach. (John Wiley & Sons, Hoboken, NJ, 2007)
-  K. McIntyre, K.G. Shojania. The challenges of quality improvements reports and the urgent need for more of them. Thorax. 2011;66:1020-1022
-  C.D. Shaw, I. Kalo. A background for national quality policies in health systems. (World Health Organization Regional Office for Europe, Copenhagen, 2002)
-  M. Kulich, M. Rosenfeld, C.H. Goss, R. Wilmott. Improved survival among young patients with cystic fibrosis. J Pediatr. 2003;142:631-636
-  N. Mayer-Hamblett, M. Rosenfeld, J. Emerson, C.H. Goss, M.L. Aitken. Developing cystic fibrosis lung transplant referral criteria using predictors of two year mortality. Am J Respir Crit Care Med. 2002;166:1550-1555
-  E.C. Dasenbrook, W. Checkley, C.A. Merlo, M.W. Konstan, N. Lechtzin, M.P. Boyle. Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis. JAMA. 2010;303:2386-2392
-  B.S. Quon, N. Mayer-Hamblett, M.L. Aitken, A.R. Smyth, C.H. Goss. Risk factors for chronic kidney disease in adults with cystic fibrosis. Am J Respir Crit Care Med. 2011;184:1147-1152
-  A. Smyth, S. Lewis, C. Bertenshaw, I. Choonara, J. McGaw, A. Watson. Case–control study of acute renal failure in patients with cystic fibrosis in the UK. Thorax. 2008;63:532-535
-  P. Chamnan, B.S. Shine, C.S. Haworth, D. Bilton, A.I. Adler. Diabetes as a determinant of mortality in cystic fibrosis. Diabetes Care. 2010;33:311-316
-  C. Johnson, S.M. Butler, M.W. Konstan, W. Morgan, M.E. Wohl. Factors influencing outcomes in cystic fibrosis: a center-based analysis. Chest. 2003;123:20-27
-  G. Döring, P. Flume, H. Heijerman, J.S. Elborn. Treatment of lung infection in patients with cystic fibrosis: current and future strategies. J Cyst Fibros. 2012;11:461-479
-  M.S. Schechter, H.H. Gutierrez. Improving the quality of care for patients with cystic fibrosis. Curr Opin Pediatr. 2010;22:296-301
-  N.C. Kraynack, M.D. Gothard, L.M. Falletta, J.T. McBride. Approach to treating cystic fibrosis pulmonary exacerbations varies widely across US CF care centers. Pediatr Pulmonol. 2011;46:870-881
-  L.S. Mott, J. Park, C.P. Murray, C.L. Gangell, N.H. de Klerk, P.J. Robinson, et al. Progression of early structural lung disease in young children with cystic fibrosis assessed using CT. Thorax. 2012;67:509-516
-  D.B. Sanders, H.J. Lai, M.J. Rock, P.M. Farrell. Comparing age of cystic fibrosis diagnosis and treatment initiation after newborn screening with two common strategies. J Cyst Fibros. 2012;11:150-153
-  J. Calvin, S.L. Hogg, D. McShane, S.A. McAuley, R. Iles, R. Ross-Russell, et al. Thirty-years of screening for cystic fibrosis in East Anglia. Arch Dis Child. 2012;97:1043-1047
-  A.M. Vernooij-van Langen, J.G. Loeber, B. Elvers, R.H. Triepels, J.J. Gille, C.P. Van der Ploeg, et al. Novel strategies in newborn screening for cystic fibrosis: a prospective controlled study. Thorax. 2012;67:289-295
-  K. Walshe. International comparisons of the quality of health care: what do they tell us?. Qual Saf Health Care. 2003;12:4-5
-  J.L. Dreachslin, M. Zernott, S. Mendenhall, E.R. Nieuwenjuijsen. Data comparability issues in international research and quality assurance. Qual Assur Health Care. 1993;5:143-156
-  E.A. Kerr, S.M. Asch, E.G. Hamilton, E.A. McGlynn (Eds.) Quality of care for general medical conditions: a review of the literature and quality indicators (RAND Corporation, Santa Monica, CA, 2000)
-  M.N. Marshall, P.G. Shekelle, E.A. McGlynn, S. Campbell, R.H. Brook, M.O. Roland. Can health care quality indicators be transferred between countries?. Qual Saf Health Care. 2003;12:8-12
-  J. Ellis. Sharing the evidence: clinical practice benchmarking to improve continuously the quality of care. J Adv Nurs. 2000;32:215-225
-  M. Goddard, R. Mannion, P. Smith. Enhancing performance in health care: a theoretical perspective on agency and the role of information. Health Econ. 2000;9:95-107
-  G. Sims. International benchmarking from Centre level cystic fibrosis data. Pediatr Pulmonol. 2010;45(S33):527
-  S. Conway, I.M. Balfour-Lynn, K. De Rijcke, P. Drevinek, J. Foweraker, T. Havermans, et al. European Cystic Fibrosis Society Standards of Care: framework for the cystic fibrosis centre. J Cyst Fibros. 2014;13:3-22
-  A. Gawande. The bell curve. N Y Ann Med. 2004; The New Yorker
-  B. Delaisi, C. Grosskopf, E. Reignault, J.M. Goehrs, J. Navarro. International registry on mucoviscidosis: comparison of the French data with the European data for 1995. Arch Pediatr. 1998;5:384-388
-  H.C. Lai, M. Corey, S. FitzSimmons, M.R. Kosorok, P.M. Farrell. Comparison of growth status of patients with cystic fibrosis between the United States and Canada. Am J Clin Nutr. 1999;69:531-538
-  A. Fogarty, R. Hubbard, J. Britton. International comparison of median age at death from cystic fibrosis. Chest. 2000;117:1656-1660
-  C. Koch, H. Cuppens, M. Rainisio, U. Madessani, H. Harms, M. Hodson, et al. European Epidemiologic Registry of Cystic Fibrosis (ERCF): comparison of major disease manifestations between patients with different classes of mutations. Pediatr Pulmonol. 2001;31:1-12
-  J. McCormick, G. Mehta, H.V. Olesen, L. Viviani, M. Macek Jr., A. Mehta, et al. Comparative demographics of the European cystic fibrosis population: a cross-sectional database analysis. Lancet. 2010;375:1007-1013
-  P.K. Knudsen, H.V. Olesen, N. Høiby, M. Johannesson, F. Karpati, B.N. Laerum, et al. Differences in prevalence and treatment of Pseudomonas aeruginosa in cystic fibrosis Centres in Denmark, Norway and Sweden. J Cyst Fibros. 2009;8:135-142
-  A.D. Jackson, L. Daly, C. Kelleher, B.C. Marshall, H.B. Quinton, L. Foley, et al. The application of current life table methods to compare cystic fibrosis median survival internationally is limited. J Cyst Fibros. 2011;10:62-65
-  P.Y. Boelle, L. Viviani, P.F. Busson, H. Olesen, S. Ravilly, M. Stern, et al. Reference percentiles for FEV1 and BMI in European children and adults with cystic fibrosis. Orphanet J Rare Dis. 2012;7:64
-  L. Viviani, A. Zolin, H.V. Olesen. ECFSPR Annual Report 2008–2009. (European Cystic Fibrosis Society Patient Registry, 2012)
-  J. McCormick, E.J. Sims, M.W. Green, G. Mehta, F. Culross, A. Mehta. Comparative analysis of Cystic Fibrosis Registry data from the UK with USA, France and Australasia. J Cyst Fibros. 2005;4:115-122
-  G. Sims. International benchmarking for cystic fibrosis patient outcomes using registry data. J Cyst Fibros. 2009;8(S2):S103
-  Cystic fibrosis data network. http://www.cysticfibrosisdata.org/metadata-and-methodology.htm
-  G. Sims. Outline and proposal for an international Cystic Fibrosis Data Network. http://www.cfww.org/programs/article/1319/Outline_and_proposal_for_an_international_Cystic_Fibrosis_Data_Network_April_2010 (April 2010)
a University Children's Hospital, Tübingen, Germany
b French CF QIP, Paris, France
c CFF Piemonte, Città della salute e della scienza, Torino, Italy
d Hospital for Sick Children, University of Toronto, Canada
e Mukoviszidose eV, Berlin, Germany
f Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington Medical Centre, Seattle, WA, USA
g CF Center, Rigshospitalet, Copenhagen, Denmark
h National Expertise CF Center, Nantes-Roscoff, France
i Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, Italy
j School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Northern Ireland, UK
k Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
© 2014 Published by Elsevier B.V.
Cystic Fibrosis Pulmonary Guidelines Chronic Medications for Maintenance of Lung Health
Peter J. Mogayzel, Jr., Edward T. Naureckas, Karen A. Robinson, Gary Mueller, Denis Hadjiliadis, Jeffrey B. Hoag, Lisa Lubsch, Leslie Hazle, Kathy Sabadosa, Bruce MarshallMon, 08/18/2014 - 18:57
American Journal of Respiratory and Critical Care Medicine
Volume 187, Issue 7, April 2013, p680-698
Cystic ﬁbrosis (CF) is an autosomal recessive disease char- acterized by abnormal airways secretions, chronic endobronchial infection,andprogressiveairwayobstruction.Theuseofmedicationsto slowtheprogressionoflungdiseasehasledtosigniﬁcantimprovement in survival. An evidence review of chronic medications for CF lung disease was performed in 2007 to provide guidance to clinicians in evaluating and selecting appropriate treatment for individuals with this disease. We have undertaken a new review of the literature to update the recommendations, including consideration of new medications and additional evidence on previously reviewed therapies. A multidisciplinary committee of experts in CF pulmonary care was established to review the evidence for use of chronic medications for CF lung disease and make treatment recommendations. Published evidence for chronic lung therapies was systematically reviewed and resulting treatment recommendations were graded based on the United States Preventive Services Task Force scheme. These guidelines provide up-to-date evidence of safety and efﬁcacy of chronic treatments of CF lung disease, including the use of novel therapies that have not previously been included in CF pulmonary guidelines.
Keywords: antibiotics; antiinﬂammatory agents; bronchodilators; CFTR modulators; hypertonic saline
To aid care providers in the use of chronic medications, the Cystic Fibrosis (CF) Foundation established the Pulmonary Clinical Practice Guidelines Committee, which published guidelines on chronic medications for the maintenance of lung heath in 2007. Since this publication, two novel medications have been approved for use in the United States and additional data have been published on therapies previously reviewed. To consider this new evidence, as well as additional and revised questions on the use of therapies, the committee conducted an assessment of the current evidence to develop the updated recommendations presented here.
Cystic Fibrosis Pulmonary Guidelines Treatment of Pulmonary Exacerbation
Patrick A. Flume, Peter J. Mogayzel, Jr., Karen A. Robinson, Christopher H. Goss, Randall L. Rosenblatt, Robert J. Kuhn, Bruce C. MarshallMon, 08/18/2014 - 18:56
American Journal of Respiratory and Critical Care Medicine, Volume 180, Issue 9, November 2009, p802-808
The natural history of cystic ﬁbrosis lung disease is one of chronic progression with intermittent episodes of acute worsening of symptoms frequently called acute pulmonary exacerbations These exacerbationstypicallywarrantmedicalintervention.Itisimportant that appropriate therapies are recommended on the basis of avail- able evidence of efﬁcacy and safety. The Cystic Fibrosis Foundation therefore established a committee to deﬁne the key questions related to pulmonary exacerbations, review the clinical evidence using an evidence-based methodology, and provide recommenda- tions to clinicians. It is hoped that these guidelines will be helpful to clinicians in the treatment of individuals with cystic ﬁbrosis.
Keywords: aminoglycosides; IV antibiotics; drug synergism; Pseudo- monas; respiratory therapy
Cystic ﬁbrosis (CF) is a complex genetic disease affecting many organs, although 85% of the mortality is a result of lung disease (1). CF lung disease begins early in life with inﬂammation and impaired mucociliary clearance and consequent chronic infec- tion of the airways (2). There is progressive decline of lung function with episodes of acute worsening of respiratory symptoms, often referred to as ‘‘pulmonary exacerbations.’’ Although a generally applicable prospective deﬁnition of a pul- monary exacerbation has not been developed, clinical features of an exacerbation may include increased cough, increased sputum production, shortness of breath, chest pain, loss of appetite, loss of weight, and lung function decline (3). Pulmo- nary exacerbations have an adverse impact on patients’ quality of life and a major impact on the overall cost of care (4). Identifying optimal treatment methods for these events could produce signiﬁcant improvements in quality and length of life for patients with CF. To identify the best treatment practices, the CF Founda- tion’s Pulmonary Therapies Committee, comprising individuals knowledgeable in all the major facets of CF care, conducted a search of published results of controlled trials of common treatment methods for exacerbations. It is not our intent to deﬁne a pulmonary exacerbation, nor to discuss relative sever- ity, but to evaluate the evidence supporting therapies and approaches for the management of a health decline determined by a CF specialist to represent an exacerbation of CF lung disease. This systematic review allowed the Committee to make speciﬁc treatment recommendations and to determine areas that need additional study. The guidelines presented are designed for general use in most individuals with CF, but should be adapted to meet speciﬁc needs as determined by the individual, their family, and their health care provider.