The History of Cystic Fibrosis by Dr James Littlewood OBE

Edited and produced by Daniel Peckham

 

1974 Crozier DN. Cystic fibrosis: a not so fatal disease. Pediatr Clin North Am 1974; 21:935-948.

This paper gives an idea of treatment at the Toronto CF clinic (figure 11) in the early Seventies. Douglas Crozier, who started the Toronto CF clinic in 1958, stated that “success of treatment will depend on a complete assessment of the patient and then continuing attempts to obtain normal bodily function and maintain it”. He described how he advised his patients to abandon the traditional low fat diet and used of very high doses of pancreatic enzymes (up to 100 Cotazym capsules per day). Crozier believed that “to deprive a child with cystic fibrosis, who usually has very little subcutaneous fat, of this important nutrient seems ridiculous”. The superior nutritional state of the Toronto patients is believed to be the main reason for their better survival. In 1973, 428 people with CF were attending the Toronto clinic of whom 92 (21.4%) were 16 years or older – this was quite remarkable for that time.

I was profoundly influenced by this landmark paper from Toronto regarding the approach to management of people with CF – also by a later visit to Henry Levison at the Toronto clinic and attendance at the 8th International Cystic Fibrosis Congress there in 1980.

 

1998 Mahadeva R, Webb K, Westerbeek RC, Carroll NR, Dodd ME, Bilton D. Clinical outcome in relation to care in centres specializing on cystic fibrosis: cross sectional study. BMJ 1998; 316:1771-1775.

This is one of the few papers which is accepted as supporting the superiority of CF Centre care to the care received at a general paediatric clinic in the local hospital. Patients at the adult cystic fibrosis centre were subdivided into three groups. Those who had received continuous care from paediatric and adult cystic fibrosis centres (group A), those who had received paediatric care at their local hospital then at an adult CF centre (group B) and those who had received neither paediatric nor adult specialist care (Group C). Body mass index was 21.3, 20.2 and 18.3 for Groups A B and C respectively (P<0.001) and the improved nutritional status was correlated with a higher FEV1 and better chest X-rays (P<0.001 for both). These findings are widely quoted as providing the first direct evidence that management in cystic fibrosis centres resulted in a better clinical outcome. This had been appreciated for years by doctors dealing with people with CF, and indeed by patients and parents, but is still contested by a minority of general paediatricians and physicians.

Professor Kevin Webb started the first CF centre for adults at Monsall Hospital Manchester in 1982; the unit later moved to the purpose-built Bradbury Unit at Wythenshawe Hospital in 1994. The CF Centre is one of the largest in the UK and the staff have made major contributions to improving CF care in the UK.

 

2003 Johnson C, Butler SM, Konstan MW, Morgan W, Wohl ME. Factors influencing outcomes in cystic fibrosis: a center based analysis. Chest 2003; 123:20-27.

The analysis was conducted using data from the Epidemiologic Study of Cystic Fibrosis from 1995 through 1996. Within-site rankings tended to be consistent across the three age groups. Patients who were treated at higher ranking sites had more frequent monitoring of their clinical status, measurements of lung function, and cultures for respiratory pathogens. These patients also received more interventions, particularly courses of IV antibiotics for pulmonary exacerbations. There were substantial differences in lung health across different CF care sites. Frequent monitoring and increased use of appropriate medications in the management of CF are associated with improved outcomes.

This study by Dr Charlie Johnson and colleagues confirmed the value of collecting data in a registry and analysis to yield valuable information. Their findings reinforce the value of more frequent monitoring and interventions in achieving better clinical outcomes.

 

2002 van Koolwijk LM, Uiterwaal CS, van der Laag J, Hoekstra JH, Gulmans VA, van der Ent CK. Treatment of children with cystic fibrosis: central, local or both? Acta Paediatr 2002; 91:972-977.

The progress of 41 totally CF Centre treated patients, 23 who came to the CF centre annually for review and 41 treated in close cooperation between the CF Centre and local hospitals. After 3 years there were no significant differences in pulmonary function, nutritional status or microbiological status. The authors conclude the results - could signify that local paediatricians have a special role in the care of patients with CF in close cooperation with the specialist centre”.

So should every patient attend a CF Centre as recommended by virtually all experienced CF clinicians since the Sixties? There is still considerable discussion on this question. This study is reassuring as it provides some support for the concept of “shared-care” which, like it or not, is still widely practised in the UK and elsewhere. There is an appropriate standard, condoned in the CF Trust’s Standards of Care document but shared care is not recommended for adults. It is possible that as regimens of treatment become more established, the standard of care at smaller local clinics will approach that at CF centres. However, there are still some children attending their local hospital with only sporadic visits to and advice from the staff at the Specialist CF Centre which is unsatisfactory. Also the numbers in this present study are small.

 

2004 Gawande A. The Bell Curve. What happens when patients find out how good their doctors really are? New Yorker, December 6th, 2004.

Although not technically a scientific paper, this is a very interesting article examining the increasingly popular question of differences in performance of various CF Centres and how this should be handled; perhaps the article should be mandatory reading for all concerned with CF care!! The subject is now a major source of interest to CF organisations such as the CF Foundation, the UK CF Trust and the European CF Society. Such differences had been documented for many years and are now receiving the attention they deserve (Woods & Piazza, 1988 above; Padman R et al. Pediatr 2007; 119:531-537).

Dr Gawande considers the methods of Dr. Warren Warwick, a successful veteran USA CF clinician, and produces a thought-provoking article along the lines of analysing the differences between the “best” and the “rest”. The differences between Centres and how to achieve optimal care is one of the current areas of interest. The USCF Foundation has estimated that if all CF Centres achieved the same results as the best CF Centres the life expectancy of their patients would increase by 7 years.

 

2007 Padman R, McColley SA, Miller DP, Konstan MW, Morgan WJ, Schechter MS, Ren CL, Wagener JS. Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Infant care patterns at epidemiologic study of cystic fibrosis sites that achieve superior childhood lung function. Pediatrics 2007; 119:e531-7.

Previous analyses of the Epidemiologic Study of Cystic Fibrosis database revealed that sites with the highest average patient lung function monitor patients more frequently and treat with antibiotics more aggressively than those where average lung function is lowest. Infants at the upper quartile sites had more office and sick visits; more respiratory tract cultures; and more frequent use of intravenous antibiotics, oral corticosteroids, mast cell stabilizers (surprisingly sodium cromoglycate still seems to be used in the USA), and mucolytics; but they received less chest physiotherapy, inhaled bronchodilators, oral nutritional supplements, and pancreatic enzymes. Data shows that both enrolment characteristics and infant care patterns are associated with lung function outcomes in later childhood. The authors suggested that pulmonary function of older children may be improved through specific interventions during the first 3 years of life.

The conclusions of this analysis are likely to be obvious to those clinicians who have seen many children permanently damaged before being eventually diagnosed as having cystic fibrosis. Also they will have noticed the contrast with those infants diagnosed and treated early after newborn screening. However, this excellent data is very welcome to convince those who are responsible for funding CF care and neonatal screening programmes and who cannot draw on clinical experience. It is interesting that in all studies of this nature over the years the more frequent use of IV antibiotics and more frequent follow-up visits are always features in the history of those with better results (Woods & Piazza, 1988 above).

 

2008 Thomas CL. O'Rourke PK. Wainwright CE. Clinical outcomes of Queensland children with cystic fibrosis: a comparison between tertiary centre and outreach services. M J Australia 2008; 188:135-139.

To evaluate and compare the clinical outcomes of children with cystic fibrosis (CF) managed primarily at a tertiary cystic fibrosis centre (CFC) with those treated at regional centres by local health care professionals and the cystic fibrosis outreach service (CFOS). A retrospective study of 273 children with CF born between 19 October 1982 and 19 February 2002 and with clinical data available between 1 January 2000 and 31 December 2002. Patients were grouped into CFC (n = 131) or CFOS (n = 142), with CFOS then further categorized into three groups depending on the level of care they received. There were no significant differences in pulmonary function, P. aeruginosa status, or height and weight z scores between children managed by CFC or by CFOS. Children receiving more care at the CFC (level of care [LOC] 1 and 2) were more likely to have multiple hospital admissions than children receiving more care in regional areas (LOC 3 and 4) (P < 0.001). The authors concluded the CFOS model provides effective delivery of specialised multidisciplinary care to children and adolescents living in rural and regional Queensland.

This is a reassuring study for the Australian families and professionals involved in this particular study. However, it is often difficult to translate the results of one study to another area or country.

 

2009 Castellani C, Southern KW, Brownlee K, Dankert Roelse J, Duff A, Farrell M, Mehta A, Munck A, Pollitt R, Sermet-Gaudelus I, Wilcken B, Ballmann M, Corbetta C, de Monestrol I, Farrell P, Feilcke M, Férec C, Gartner S, Gaskin K, Hammermann J, Kashirskaya N, Loeber G, Macek M Jr, Mehta G, Reiman A, Rizzotti P, Sammon A, Sands D, Smyth A, Sommerburg O, Torresani T, Travert G, Vernooij A, Elborn S. European best practice guidelines for cystic fibrosis neonatal screening. J Cyst Fibros 2009; 8:153-173.

A European document full of good advice. When starting a newborn screening programme for CF it is important to take precautions in order to minimise avoidable risks and maximise benefits. In Europe more than 25 screening programmes have been developed, with quite marked variation in protocol design. CF centre care and the availability of necessary medication are essential prerequisites before the introduction of newborn screening programmes. It is essential that early diagnosis is followed by optimal treatment.

 

2009 Simmonds NJ, Cullinan P, Hodson ME. Growing old with cystic fibrosis - the characteristics of long-term survivors of cystic fibrosis. Respir Med 2009; 103:629-635.

The proportion of patients with cystic fibrosis (CF) who are middle-aged is increasing - and is likely to continue to do so. We surveyed a population of long-term CF survivors to assess their burden of illness and profile their disease characteristics. The full spectrum of disease is represented in this population and, importantly, 30% are DeltaF508 homozygous. Provision needs to be made for the healthcare needs of this increasing population of older patients.

This is invaluable experience from the largest adult CF centre in the world.

 

2009 Huffmyer JL, Littlewood KE, Nemergut EC. Perioperative management of the adult with cystic fibrosis. Anesth Analg 2009; 109:1949-1961.

A useful review article on the optimal perioperative management of patients with CF requires an understanding of the relevant pathophysiology and the unique challenges presented by these patients. The authors reviewed these concepts, including special considerations such as liver and lung transplantation and pregnancy.

These are particularly important as not infrequently a person with CF is admitted to a surgical unit where there is limited knowledge of CF - for example postoperatively enzymes may be omitted leading to DIOS and serious unnecessary complications.

 

2009 Lebecque P, Leonard A, De Boeck K, De Baets F, Malfroot A, Casimir G, Desager K, Godding V, Leal T. Early referral to cystic fibrosis specialist centre impacts on respiratory outcome. J Cyst Fibros 2009; 8:26-30.

Published studies concerning the impact of specialist care on lung disease in cystic fibrosis remain limited and most are either biased due to comparison with historical controls and/or underpowered. In this retrospective multicentre study, data from all CF children fulfilling the following criteria were collected: 1) Age 6yr and less than 18 yrs at the end of 2003; 2) diagnosed before 8 yrs; 3) follow-up in an accredited Belgian CF centre; 4) at least 1 spirometry and respiratory culture available for 2003. Group A included children referred 2 yrs or more after the diagnosis. Patients from Group A were then matched with a single early referred patient on the basis of 2 criteria: same centre, as closest age as possible (Group B). Data from 217 children were collected (Group A: 67). Late referred patients had a lower FEV1 (77.2%+/-22.4 vs 86.7% +/-19.4, p=0.01) and a higher prevalence of P. aeruginosa (38.6 vs 17.5%, p<0.05).

So in this population of CF children, a delay of 6.1 yr (vs 0.1 y) between diagnosis and referral to a specialist clinic resulted in poorer respiratory outcome at age 13 years. Most experienced CF clinicians are convinced that CF centre care is the ideal but all are not convinced.

 

2009 Borowitz D, Robinson KA, Rosenfeld M, Davis SD, Sabadosa KA, Spear SL, Michel SH, Parad RB, White TB, Farrell PM, Marshall BC, Accurso FJ. Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatrics 2009; 155(6 Suppl):S73-93.

This consensus document states the focus of management is on maintaining health by preventing nutritional and respiratory complications. The CF Foundation convened a committee to develop recommendations based on a systematic review of the evidence and expert opinion. These guidelines encompass monitoring and treatment recommendations for infants diagnosed with CF and are intended to help guide families, primary care providers, and specialty care centers in the care of infants with CF.

 

2009 Post PN, Wittenberg J, Burgers JS. Do specialized centers and specialists produce better outcomes for patients with chronic diseases than primary care generalists? A systematic review. Int J Qual Health Care 2009; 21:387-396.

The authors searched Embase from 1987 through March 2008 for studies reporting the effect of treatment in a specialized or high-volume center or by subspecialists on clinically relevant outcomes. The authors concluded the available literature suggests that among patients with rheumatoid arthritis, diabetes mellitus or cystic fibrosis, outcomes are not superior in specialized centers or with subspecialists compared with other forms of chronic illness care.

This type of the Cochrane Review type, is of some concern where a conclusion is based merely on the published work that reviewers, who may be of relatively limited clinical experience, come to a conclusion which different to that of generations of CF physicians and families. It would be more helpful if reviewers were to assess all the evidence, not merely only the trials which come up to their rigorous academic standards. Although it is unlikely that studies of this type will affect experienced clinician's firm conviction that centre care is preferable to local hospital care for people with CF, it is of some concern is that such a study may be used by health care providers to deny patients funding to attend a specialist CF centre as has occurred in the past.

 

2009 Miller AR, Condin CJ, McKellin WH, Shaw N, Klassen AF, Sheps S. Continuity of care for children with complex chronic health conditions: parents' perspectives. BMC Health Services Research. 2009; 9:242.

Continuity of care has been explored largely from academic and service provider perspectives, and in relation to adult patient/client groups. the authors interviewed parents of children with complex chronic health conditions to examine how their experiences and perceptions of continuity of care fit with these perspectives; and to identify the salient factors in the experience of, and factors contributing to, continuity in this population.

A thorough knowledge of the child on the part of service providers emerged as extremely important to parents; such knowledge was underpinned by continuity of personal relationships, principally, and also by written information. For this population, notions of continuity extend to the full range of service providers these children and families need to achieve optimal health status, and are not limited to physicians and nurses. Communication among providers was seen as integral to perceived continuity. Compartmentalization of services and information led to parents assuming a necessary, though at times, uncomfortable, coordinating role. Geographic factors, institutional structures and practices, provider attitudes, and, on occasion, parent preferences and judgments, were all found to create barriers to "seamless" management and provision of care continuity across providers, settings, and sectors.

Although the authors suggest that "These findings add new perspectives to the understanding of continuity within chronically ill children's health care. They are relevant to contemporary initiatives to improve continuity of services to children with special health care needs, demonstrate the need for parental support of their important role in maintaining continuity, and suggest avenues for further research", they are of course the basic principles upon which good care for CF is organised in the best CF centres.

Undoubtedly lack of continuity of care is one of the major deficiencies of the UK National Health Service.

 

2010 Webb AK, Dudley-Southern R, Jones AM. Development of a modern adult cystic fibrosis centre in Manchester. J R Soc Med 2010; 103 Suppl 1:S15-19.

An interesting account of the development of the Manchester Adult CF Centre in the North of England from its beginning in 1982 to care for the 30 or so adults still attending paediatric clinics in the city at that time to the present large purpose built centre opened in September 2009.

The stormy course is described by Professor Kevin Webb who, with Mary Dodd CBE the physiotherapist, has been responsible for driving the development forward and building up an internationally recognised Adult CF Service at the UHSM Manchester Adult Cystic Fibrosis Centre. In recent years the consultant team has been joined by Dr Andy Jones and Dr Rowland Bright-Thomas

 

2010 Schechter MS, Gutierrez HH. Improving the quality of care for patients with cystic fibrosis. Curr Opin Pediatrics 2010; 22:296-301.

This article describes the factors that have contributed to the recent acceleration in this improvement in care and the important role of the Cystic Fibrosis Foundation. Initiatives considered to improve CF care over the past decade include the refinement of a sophisticated patient registry that allows a comparison of center processes and outcomes; development of evidence-based and consensus-based guidelines regarding standards of care; cultural transformation, including the training of care center teams in a systems-oriented approach to quality improvement; data transparency; and encouragement of a patient-centered and family-centered orientation. Cystic Fibrosis Foundation initiatives have promoted an increase in the consistent provision of evidence-based care and the promulgation of innovative, proactive therapeutic approaches. Unfortunately, so far most of these accomplishments have not been documented in peer-reviewed research articles, but rather in platform presentations at national meetings, meeting abstracts, data reports to center directors, and published reports from individual centers. While several new medications for CF lung disease have been introduced in the last decade, improvements in outcomes have been largely due to refinements in the delivery of care. At this point, the most efficient and reliably effective technique for promoting further improvement still needs to be identified. Recent discussions have centered on attempts at new innovative approaches that utilize more selective teaching of relevant systems-based quality improvement methods in the specific CF environment.

 

 

Simmonds NJ, Macneill SJ, Cullinan P, Hodson ME. Cystic fibrosis and survival to 40 years: a case-control study. Eur Respir J 2010; 36:1277-1283. [PubMed]
A case-control study of adult CF patients from the Royal Brompton, London was used to compare long-term survivors (aged >= 40 yrs) with patients who died before reaching 30 yrs of age. Factors resulting in increased probabilities of survival included high body mass index, respiratory function tests on transfer from the paediatric clinics and the exclusive use of oral antibiotics. Factors resulting in decreased probabilities of survival were Pseudomonas aeruginosa acquisition or pneumothorax before transfer to the adult clinic and referral from a paediatric clinic in a deprived area. Long-term survival is associated with the clinical features present by the time of referral to an adult clinic.

 

This study, from the world's largest adult CF clinic, confirms the expected factors which are associated with longer survival. They are predictable and include better nourishment and respiratory function tests without need for courses of intravenous antibiotics. The relationship to Pseudomonas was be expected and the influence of social deprivation so obvious for so long to clinicians dealing with patients is confirmed. So nothing new but nice to have the facts confirmed.

These authors later showed that longer survival was not associated with increased residual CFTR function (Simmonds NJ et al. Eur Respir J 2011; 37:1076-1082). [PubMed]

 

Stern M, Niemann N, Wieddemann B, Wenzlaff P, on behalf of the German CFQA Group. Benchmarking improves quality in cystic fibrosis care: a pilot project involving 12 centres. Int J Qual health Care 2011; 23:349-56.[PubMed] (Full text is available to download via PubMed entry)
A group of 12 CF centres in Germany, treating a total of 1200 patients of all ages, enrolled in a nationwide pilot benchmarking project from 2004 to 2007. Key nutritional and respiratory parameters were used as quality indicators. Numerical benchmarks were set and used for ranking. Applying the plan-do-check-act cycle, quality improvement interventions were introduced, such as harmonization of definitions and references, improvement of measurement standards, data quality, completion of missing data, enforcement of early aggressive antibiotic treatment and individual adaptation of dietary counselling. Ranking alone was not sufficient for identification of the best performing centres unless it was accompanied by longitudinal follow-up. Improvement was possible in the 3 years' period as shown by benchmarking for single centres that introduced new interventions in nutritional and antibiotic treatment most consequently.
CF provides a model of the link between processes of health care delivery and health outcomes of patients. Quality improvement is a continuous goal in CF care with realistic potential as exemplified by our data. Accountability was introduced and transparency was improved by our pilot benchmarking project. Using the benchmarking procedure, our long-term project will reinforce standards, programmes, and individual attitudes and principles to ensure continuous quality improvement in CF health care

 

2011 Barr HL, Britton J, Smyth AR, Fogarty AW. Association between socioeconomic status, sex, and age at death from cystic fibrosis in England and Wales (1959 to 2008): cross sectional study. BMJ 2011; 343:d4662.

To determine the trend in the association between socioeconomic status and sex and median age at death from cystic fibrosis in England and Wales, over the past 50 years. From 1959 to 2008, 6750 deaths were attributed to cystic fibrosis in England and Wales. Males were more likely to die above the annual median age at death than females (from 1959 to 1999, adjusted odds ratio for socioeconomic status 1.28, 95% confidence intervals 1.13 to 1.45; from 2000 to 2008, 1.57, 1.18 to 2.08). Individuals in the highest socioeconomic class were also more likely to die above the median age of death than those in the lowest socioeconomic class (from 1959 to 2000, adjusted odds ratio for sex 2.50, 2.16 to 2.90; from 2001 to 2008, 1.89, 1.20 to 2.97). The authors concluded that socioeconomic status and sex remain strong determinants of survival from cystic fibrosis in England and Wales, and the magnitude of these effects does not appear to have substantially reduced over time.

An article from an experienced team in Nottingham providing evidence for the relationship that poor socioeconomic factors and female sex are both associated with a lower median age of death in the UK. There was a recent similar study from USA by Michael Schechter (Schechter MS et al. J Pediatr 2009; 155:634-639. ). Both these studies provide firm evidence of the association of socioeconomic status and survival - although this had been apparent to clinicians for many years.

 

2011 Briesacher BA, Quittner AL, Fouayzi H, Zhang J, Swensen A. Nationwide trends in the medical care costs of privately insured patients with cystic fibrosis (CF), 2001-2007. Pediatr Pulmonol 2011; 46:770-776.

The authors identified 3,273 individuals with CF between 2001 and 2007. Overall, the costs of prescription drugs, outpatient visits, and durable medical equipment increased by 59% during the 7-year period ($18,715 in 2001 vs. $29,718 in 2007, P < 0.001). The proportion of individuals hospitalized increased from 24.0% to 38.9%, P < 0.001. Annual testing of pulmonary function increased 53% (49.9% in 2001 to 76.3% in 2007, P < 0.001) and respiratory cultures more than doubled (27.9-67.5%, P < 0.001). Use of CF-related therapies also significantly increased (dornase alfa, 32.1-52.4%, P < 0.001; oral antibiotics, 54.1-71.8%, P = 0.007). Analyses by age showed the largest increases in total medical care costs occurred for the oldest CF patients (aged >30; $20,536 in 2001 to $56,116 in 2007, P < 0.001) and the youngest (aged <11; $3,060 in 2001 to $31,723 in 2007, P < 0.001). The authors concluded that although improvements in diagnosis and treatment have yielded substantial benefits, they have come at considerable cost, both in terms of treatment burden and health care dollars.

The cost of care has received increasing attention as more patients survived for longer and more increasingly expensive therapies became available. These figures relate to the USA but similar data have been collected recently in the UK by the CF Trust. In 2000 I collaborated with an accountant from our Finance Department, Elaine Cross, to estimate the cost of the St James Leeds CF service. This was possible as by this time we had complete patient data of our 161 children on full care at the centre computerised and the cost related to 1996 (Littlewood & Cross. Present day treatment of cystic fibrosis: its content and cost. In Bodger K, Daly M, Heatley RV. Eds. Clinical Economics in Gastroenterology. Blackwell Science 2000:220-249). The annual cost for our whole clinic of 161 children was £1,701,234 or an average of £10,567 per patient in 1996. Recent data collected by the CF Trust shows that cost has increased in the UK in a similar manner to that reported in this 2011 study. Undoubtedly the rising cost, which will occur with the availability of new treatments to correct or nullify the effects of the various mutations, will prove to be a major problem.

 

2011 Colombo C, Littlewood J. The implementation of standards of care in Europe: state of the art. [Review] J Cyst Fibros 2011; 10 Suppl 2:S7-15.

We reported the care and condition of people with cystic fibrosis (CF) in 34 European countries using data obtained from publications, registries and professionals providing CF patient care. Care and outcomes differ markedly between countries. Although the 2005 European standards of patient care publication was widely known, in many countries there were no specialized CF centres. In only a minority of countries was funding considered adequate and in some countries costs covered by patients compromised care. Only 15 countries had a national CF patient registry. Neonatal screening was routine in only 10 countries, but this did included 59% of European infants. Suggestions for the future include at least one adequately staffed CF Centre in each country, improved funding, neonatal screening, national patient registries and the formation of national CF parent and patient organizations.

Carla Colombo and myself collected much of this information by personal contact with clinicians in Europe to whom we are grateful. The standard of care was very variable and the resources allocated to CF care also varied considerably.

 

2012 Mc Ewan FA. Hodson ME. Simmonds NJ. The prevalence of "risky behaviour" in adults with cystic fibrosis. J Cyst Fibros 2012; 11:56-58.

The prevalence of "risky-behaviour" including alcohol and illicit drug use, smoking and unprotected sexual intercourse, of adults with cystic fibrosis (CF) is unknown. We conducted this prospective questionnaire-based study to further explore this issue. METHODS: An anonymous 71-point questionnaire was sent to all adult patients aged >=18 years attending the Royal Brompton CF Unit. Results were compared to national (non-CF) data. RESULTS: 83% (n=151) drink alcohol and 13% (n=23) drink more than recommended by national guidelines. 46% (n=84) have tried smoking and 3% (n=5) continue to smoke regularly. 35% (n=64) have tried illicit drugs and 3% (n=6) continue to use them. 86% (n=154) are sexually active; 60% use contraception (males 46%, females 62%). Compared with the general (non-CF) UK population, less CF patients drink heavily (13 vs. 23%; p<0.001), smoke (3 vs. 21%; p<0.001), have tried illicit drugs (35 vs. 37%; p<0.001) and are sexually active (86 vs. 97%; p<0.001).The same proportion use contraception (60 vs. 61%; p=0.8). The authors conclude that participation in risky behaviour was modest. With improved life expectancy this may increase. Awareness of this is important so that health promotion measures can be introduced early.

An interesting study from the world's largest Adult CF clinic at the Royal Brompton in London. Adults with CF seem to have the same degree of "risky habits" as the non-CF populations except, understandably, very few of them smoke.

 

2012 Doull I, Evans H. South and Mid Wales Paediatric Cystic Fibrosis Network. Full, shared and hybrid paediatric care for cystic fibrosis in South and Mid Wales. Arch Dis Child 2012; 97:17-20.[PubMed]

Although care for children with cystic fibrosis (CF) is increasingly shared between CF centres and local CF clinics, the optimal model is unclear. The authors compared three models of care within a well established CF network: full centre care; local clinic based care with annual review by the CF centre; and hybrid care, where the child is usually reviewed at least three times a year by the specialist CF centre.

Of 199 children and young people with CF in South and Mid Wales, 77 were receiving full care, 102 shared care and 20 hybrid care. There were no significant differences in baseline characteristics, nutritional outcomes or use of chronic therapies. There was however a statistically significant difference between full, shared and hybrid care in mean forced expiratory volume in 1 s (FEV(1)) per cent predicted (89.2% vs 74.5% vs 88.9%; p=0.001).

The authors concluded these differences in pulmonary function are likely to reflect the model of care received, and may affect long term outcomes.

This important study shows an advantage for children who received all their care at the Wales CF Centre in Cardiff however the results were not accepted by all Iolo Doull's colleagues in Wales and drew a vigorous response from paediatricians working in the local CF clinics in Newport (Bowler I, Pierrepoint M, Evans R. Arch Dis Child 2012; 97:88) and Lanarkshire (Dryden C et al. Arch Dis Child 2012; 97: 88-89).

So the discussion continues in the UK as to whether CF centre care is superior to care shared between a CF Centre and a local hospital clinic.

 


Boyle MP. Sabadosa KA. Quinton HB. Marshall BC. Schechter MS. Key findings of the US Cystic Fibrosis Foundation's clinical practice benchmarking project. Quality & Safety 2014; 23 Suppl 1:i15-i22.[PubMed]
Benchmarking is the process of using outcome data to identify high-performing centres and determine practices associated with their outstanding performance. The US Cystic Fibrosis Foundation (CFF) Patient Registry contains centre-specific outcomes data for all CFF-certified paediatric and adult cystic fibrosis (CF) care programmes in the USA. The CFF benchmarking project analysed these registry data, adjusting for differences in patient case mix known to influence outcomes, and identified the top-performing US paediatric and adult CF care programmes for pulmonary and nutritional outcomes. Separate multidisciplinary paediatric and adult benchmarking teams each visited 10 CF care programmes, five in the top quintile for pulmonary outcomes and five in the top quintile for nutritional outcomes. Key practice patterns and approaches present in both paediatric and adult programmes with outstanding clinical outcomes were identified and could be summarised as systems, attitudes, practices, patient/family empowerment and projects. These included: (1) the presence of strong leadership and a well-functioning care team working with a systematic approach to providing consistent care; (2) high expectations for outcomes among providers and families; (3) early and aggressive management of clinical declines, avoiding reliance on 'rescues'; and (4) patients/families that were engaged, empowered and well informed on disease management and its rationale. In summary, assessment of practice patterns at CF care centres with top-quintile pulmonary and nutritional outcomes provides insight into characteristic practices that may aid in optimising patient outcomes.
This study has clearly identified the characteristics of good CF care with which few would disagree - strong leadership, high expectations, early and aggressive management and engaged, empowered, well-informed families.

 

2014 Chuang S. Doumit M. McDonald R. Hennessy E. Katz T. Jaffe A. Annual Review Clinic improves care in children with cystic fibrosis. J Cyst Fibros 2014; 13(2):186-9. 24091167+[PubMed]
It is unclear whether annual multidisciplinary reviews in cystic fibrosis (CF) patients should be conducted in dedicated annual review (AR) clinics or during continuous assessments throughout the year. The aim of this study was to assess the effect of introducing an AR clinic.
A retrospective written and electronic record review of CF patients was carried out for 2007 (no AR Clinic) and 2010 (established AR Clinic) calendar years. An internet-based satisfaction survey was distributed to families attending the AR clinic.
In total, 123 children (mean age 9.5 years, range 1.32-18.8 years) and 141 children (8.3 years, 1.1-18.3 years) were included in 2007 and 2010 respectively. There was a significant increase in multidisciplinary reviews (documented annual review 28% vs 85%, P < 0.001; dietary assessment 46% vs 92%, P < 0.001) and investigations (OGTT 2% vs 74%, P < 0.001; abdominal ultrasound 35% vs 85%, P < 0.001) conducted after the introduction of AR clinic. The majority of the families surveyed (85%) were satisfied or very satisfied with the AR clinic. The authors concluded that a CF AR clinic significantly improves the number of annual investigations and multidisciplinary reviews performed. Families were satisfied with this new process.
 
Annual reviews have been routine in the Leeds CF clinics since the early Eighties. We reported favourable experience with reviews in a number of publications (Littlewood JM, Kelleher J, Rawson I, Gilbert J, Firth J, Morton S, Wall C. Comprehensive assessment of patients at a CF centre identifies suboptimal treatment and improves management, symptoms and conditions. 10th International Cystic Fibrosis Congress, Sydney 1988 Excerpta Medica Asia Pacific Services. 89-90) and in 1993 (Littlewood JM. The value of comprehensive assessment and investigation in the management of cystic fibrosis. In Clinical Ecology of Cystic Fibrosis. H Escobar, CF Baquero Suarez (Eds). Elsevier Science Publishers. 1993:181-187). Most subsequent publications have found the process useful and acceptable to both parents and patients. The provision of Comprehensive Cystic Fibrosis Assessments (Annual Assessments) with detailed advice on treatment, was the reason for the build up and popularity of the Leeds CF Centre during the Eighties and subsequently.
See also Littlewood et al in 1988 and 1993 sections of this History for further details of early Leeds work on comprehensive assessments.

 

2014 Conway S. Balfour-Lynn IM. De Rijcke K. Drevinek P. Foweraker J. Havermans T. Heijerman H. Lannefors L. Lindblad A. Macek M. Madge S. Moran M. Morrison L. Morton A. Noordhoek J. Sands D. Vertommen A. Peckham D. European Cystic Fibrosis Society Standards of Care: Framework for the Cystic Fibrosis Centre. J Cyst Fibros 2014; 13 Suppl 1:S3-22. [PubMed]
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 recognised 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. This document is welcome as, surprisingly, there are still occasional consultants in the UK who question the need for CF centre care.

 

2014 MacKenzie T. Gifford AH. Sabadosa KA. Quinton HB. Knapp EA. Goss CH. Marshall BC. Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival analysis of the cystic fibrosis foundation patient registry. Ann Int Med 2014; 161:233-41.[PubMed]
Between 2000 and 2010, the number of patients in the Cystic Fibrosis Foundation Registry (CFFPR) increased from 21,000 to 26,000, median age increased from 14.3 to 16.7 years, and adjusted mortality decreased by 1.8% per year (95% CI, 0.5% to 2.7%). Males had a 19% (CI, 13% to 24%) lower adjusted risk for death than females. Median survival of children born and diagnosed with CF in 2010 is projected to be 37 years (CI, 35 to 39 years) for females and 40 years (CI, 39 to 42 years) for males if mortality remains at 2010 levels and more than 50 years if mortality continues to decrease at the rate observed between 2000 and 2010.
The authors concluded that children born and diagnosed with CF in the United States in 2010 are expected to live longer than those born earlier. This has important implications for prognostic discussions and suggests that the health care system should anticipate greater numbers of adults with CF.

 

Middleton PG. Wagenaar M. Matson AG. Craig ME. Holmes-Walker DJ. Katz T. Hameed S. Australian standards of care for cystic fibrosis related diabetes. Respirology 2014; 19:185-92. 24372844
This document seeks to combine various guidelines to provide an Australian approach to the management of CFRD and establish the guidelines within the Australian CF Standards of Care. It is intended that this document will provide assistance to doctors, nurses, dietitians, physiotherapists, diabetes educators and CF patients concerning the issues surrounding CFRD, and it will be reviewed and updated in 2016.

 

2014 Saiman L. Siegel JD. LiPuma JJ. Brown RF. Bryson EA. Chambers MJ. Downer VS. Fliege J. Hazle LA. Jain M. Marshall BC. O'Malley C. Pattee SR. Potter-Bynoe G. Reid S. Robinson KA. Sabadosa KA. Schmidt HJ. Tullis E. Webber J. Weber DJ. Infection prevention and control guideline for cystic fibrosis: 2013 update. Control & Hospital Epidemiology 2014; 35 Suppl 1:S1-S67.
Latest US guidelines.

 

2004 Smyth AR. Bell SC. Bojcin S. Bryon M. Duff A. Flume P. Kashirskaya N. Munck A. Ratjen F. Schwarzenberg SJ. Sermet-Gaudelus I. Southern KW. Taccetti G. Ullrich G. Wolfe S. European Cystic Fibrosis Society Standards of Care: Best Practice guidelines. J Cyst Fibros 2014; 13 Suppl 1:S23-42. Full text available on the ECFS website.[PubMed]
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. The current document builds on this work, setting standards for best practice in key aspects of CF care. The objective of the 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 of the full version..
The authors 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.

 

 


2014 Stern M. Bertrand DP. Bignamini E. Corey M. Dembski B. Goss CH. Pressler T. Rault G. Viviani L. Elborn JS. Castellani C. European Cystic Fibrosis Society Standards of Care: Quality Management in cystic fibrosis. J Cyst Fibros 2014; 13 Suppl 1:S43-59.[PubMed]

Full text available on the ECFS website.
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 with particular reference to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons.

 


Elborn JS, Bell SC, Madge SL, Burgel PR, Castellani C, Conway S, De Rijcke K, Dembski B, Drevinek P, Heijerman HG, Innes JA, Lindblad A, Marshall B, Olesen HV, Reimann AL, Solé A, Viviani L, Wagner TO, Welte T, Blasi F. Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis.  Eur Respir J. 2016 Feb; 47(2):420-8. doi: 10.1183/13993003.00592-2015. Epub 2015 Oct 9.
[PubMed]

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.
Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life- threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly recommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.
 
- The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme.

 


Mogayzel PJ Jr, Dunitz J, Marrow LC, Hazle LA.  Improving chronic care delivery and outcomes: the impact of the cystic fibrosis Care Center Network.  BMJ Qual Saf. 2014;23 Suppl 1:i3-8. doi: 10.1136/bmjqs-2013-002363.  [PubMed]    
    
In 1999, analysis of data from the CF Foundation's Patient Registry detected variation in care practices and outcomes across centres, identifying opportunities for improvement. In 2002, the CF Foundation launched a comprehensive quality improvement (QI) initiative to enhance care by assembling national experts to develop a strategic plan to disseminate QI training and processes throughout the Care Center Network. The QI strategies included developing leadership (nationally and within each care centre), identifying best CF care practices, and incorporating people with CF and their families into improvement efforts. The goal was to improve the care for every person with CF in the USA. Multiple tactics were undertaken to implement the strategic plan and disseminate QI training and tools throughout the Care Center Network. In addition, strategies to foster collaboration between care centre staff and individuals with CF and their families became a cornerstone of QI efforts.
Today it is clear that the application of QI principles within the CF Care Center Network has improved adherence to clinical guidelines and achievement of important health outcomes.

 

 

Kopp BT, Nicholson L, Paul G, Tobias J, Ramanathan C, Hayes D Jr. Geographic variations in cystic fibrosis: An analysis of the U.S. CF Foundation Registry. Pediatr Pulmonol. 2015 Mar 30. doi: 10.1002/ppul.23185. [Epub ahead of print] [PubMed]
Emerging evidence suggests that the prevalence of pathogens common in cystic fibrosis (CF) may be unevenly distributed across the United States (U.S.). Data were analyzed from the 30,896 subjects in the U.S. CF Foundation Patient Registry during the years 2007-2012, via geographical grouping of states based upon the Nationwide Inpatient Sample classification.
Significant differences in racial distribution were seen, including half of the total U.S. African-American CFulation residing in the South. Both African-Americans and Hispanics had increased Medicaid usage (52.2%, 41.8%, respectively). Culture-reported pathogens were markedly different across the U.S., with the highest percentage of patients with Methicillin-resistant Staphylococcus aureus (41.9%), Pseudomonas aeruginosa (71.2%), and non-tuberculous mycobacterium (10.0%) in the South. The South region also had the lowest mean body mass index and forced expiratory volume in one second. Chronic medication usage such as inhaled tobramycin or macrolides followed P. aeruginosa distribution, while inhaled dornase alfa was most used in the West (84.7%). Co-morbid conditions varied, with the highest percentage of depressed subjects in the Midwest (18.3%). Mean regional mortality rates were not statistically different among regions, although highest in each age grouping of the South.
The authors concluded the U.S. has significant regional variations in CF demographics, insurance, pathogens, medication usage, and co-morbidities, without an overall impact on regional mortality. They suggest that regional variations in care practices should be studied further based on the findings.