Adult Care in Cystic Fibrosis
Abstract
Cystic fibrosis (CF) is now more common in adults than children in countries with well- developed health care systems. The number of adults continues to increase and will further increase if the new cystic fibrosis transmembrane conductance regulator (CFTR) modulators are disease modifying. Most of the complex morbidity and almost all the mortality of CF occur in adults and will increasingly follow this pattern even with new effective modulator therapies. Maintaining good quality of life including social functioning and maximizing survival for adults are the key priorities. This requires a highly knowledgeable and adaptable multidisciplinary team, which, though focused on maintaining lung health, requires an increasing range of other disciplines and special- ties to maximize well-being. Changes in health care systems will require current models of care to adapt to provide care for the large number of adult patients. With increasing survival and age, many are likely to have both CF morbidities and additional diseases of aging. New models are needed for health care delivery for this expanding population with complex medical conditions.
Keywords
► cystic fibrosis
► adults
► multidisciplinary team
► CFTR dysfunction
► comorbidities
Cystic fibrosis (CF) has transformed over the past six decades from a disease exclusively affecting children to now being a disease affecting majority of adults (>16 years) in developed countries.1 Predicted median survival is now in the late forties, and it is very unusual for children to die or require lung transplantation from the pulmonary consequences of the disease.1–4 This change in demography requires a step- change in the delivery of care from predominantly a pediatric environment to integrated adult services to deliver complex multisystem care.1,4,5 Adult care programs are well developed in many countries, but surprisingly many CF clinics for adults are delivered primarily by pediatricians as an exten- sion of a pediatric program.6 It is unlikely that this model will be sustainable or will meet the increasingly complex needs of an aging population of adults with CF.1
Transition to adult care is one of the first of many challenging nodes in the life of a person with CF.7,8 Navigat- ing a new care program, often with a different philosophy and at the same time emerging from the teenage years into adulthood, is frequently challenging.8 This often coincides with some disease progression and/or the development of complications of CF. The period of transition to adult care is associated in almost all registries with a decline in forced expiratory volume in 1 second (FEV1) (►Fig. 1).9 Adjusting into long-term care in an adult health care environment with increased responsibility provides an opportunity for collab- orative partnership and the management of this disease with people with CF, their carers, and multidisciplinary teams (MDTs).7,8 This care is optimal when focused on empowering adults with CF to fully engage in all aspects of adult life, such as education, work, sport, leisure, relationships, and family life. The incremental burden of care over time to deal with progressive lung disease and other complications of cystic fibrosis transmembrane conductance regulator (CFTR) dys- function are major challenges for people with CF and the MDTs providing care. Other concomitant medical conditions associated with aging are also developing and multifactorial and contributed to by CFTR dysfunction, proaging effects of chronic inflammation, a lifelong high energy (fat) diet, and other external factors.1,5,10–12
The recent introduction of CFTR modulators is likely to further improve survival and significantly change the natural history of disease.1,13 In those with preserved lung function and structure, CFTR modulators are likely to reduce the rate of progression and maintain good health for prolonged periods. This group may need less symptomatic treatment such as airways clearance or complex inhaled antibiotic regimes than they are currently using.14 Individuals with moderate lung disease are likely to stabilize and progress more slowly. However, they may still require other adjunct therapies for airway mucus clearance and treatment of infection. Those with advanced CF lung disease (ACFLD) may stabilize but still need the full gambit of current thera- pies or require transplantation at an older age, a trend already evident before they were available.15
The combination of an increasingly well adult population, though still with a life-limiting condition, will create new tensions to balance the enormous burden of care for people with CF and the desire to live full and fulfilling lives in the face of slow but progressive deterioration of health due to lung disease or other complications. This presents CF health care teams with a challenging but hugely rewarding taskof working with people with CF to maximize their survival, quality of life, and ability to contribute to society while maintaining optimal health. Achieving this will be through making rational, in- formed decisions, which often require compromise and ad- justment by both health care professionals and patients. This should be informed by best evidence from clinical research, from randomized controlled trials, and increasingly from rich, real-world evidence generated through the high fidelity regis- tries available now in many countries with longitudinal data on patients.16 International and national guidelines on the optimal management of many aspects of CF care are widely available and should be used to direct and challenge CF MDTs and inform people with CF so that optimal decisions can be
made with the support and mentorship of the health care team.14,17–22 As CF is a long-term condition and there is an
opportunity for health care teams to develop very informed therapeutic relationships with the patients this brings with it challenges of boundaries and emotional cost to CF teams of delivering often complex and emotionally intensive care.23,24
In this article, some of the issues around the provision of care for adults with CF will be explored, with an emphasis on areas of challenge or growth. These will focus on the health care and wider societal needs of people with CF. Health care and life mutually interact and should be considered when providing care in CF.25 There are numerous high-quality recent reviews of the specifics of CF care and international guidelines available to help MDTs and people with CF and to discuss treatment options and optimize care at any particu- lar juncture of the natural history of this disease in a particular individual. This review will not cover these spe- cific areas but will signpost appropriate reviews and guide- lines. The overall aim of this review is to provide a provocative summary of the challenges that we face in the current provision of care and to look forward to future developments with increasing numbers of adults who will have less morbidity and longer survival. This will require creative thinking in CF teams to ensure the future provision of the best quality care for this group of patients.
Demographics of Cystic Fibrosis
There are currently at least 80,000 people with CF recorded on registries.1,26 This largely reflects patients in Europe and North
America and Australia. The numbers of patients in South America, Africa, and Asia are less complete, but in many of these countries and continents, registries are developing to determine the number of patients and explore the natural history in different health care systems.26 There is clear evi- dence of different demographics in middle- to high-income countries compared with countries with a low national in- come.27 This has been explored in Europe and demonstrates that western countries have many more adults than countries in the eastern part of Europe, which have much lower expenditures on health care and have health care systems which are less developed for the care of people with rare diseases and long-term conditions such as CF.27,28 Within countries, there is also strong evidence that low socioeconomic status of individuals has a very strong relationship with reduced survival and increased morbidity.29–31 For a child with CF, low socio economic status is associated more strongly with poor outcomes than any other factor. Social, country, and continental inequal- ities in health care will continue to be a major factor in the outcome for people with CF and will have a major impact on the natural history and the morbidity encountered by adults.32
Inequality of provision of care will be further amplified by high- cost CFTR modulator drugs such as lumacaftor/ivacaftor and tezacaftor/ivacaftor, which, at the current time, are not available in all countries including the United Kingdom and Canada.33With the improving survival for people with CF and an increasing number of adults surviving to their thirties and forties. Several studies have used modeling to estimate what this growth is likely to be over the next 15 to 20 years2,34,35 (►Fig. 2). The studies suggest that the number of children with CF will increase marginally due to identification through neonatal screening programs.1,2,36 However, as screening
programs are introduced in Asia, Africa, and South America, many more children may be identified.37,38 In contrast, there will be substantial increases in the number of adults with CF, with potentially around 50% increase in numbers over the next 20 years.34 These increases are a result of optimal care through pediatric and adult centers, with fewer children now dying because of CF and the median age of death progressively increasing in the adult population. The assumptions made in the studies do not include the impact of CFTR modulators,which, as they become widely available, will further increase the number of adults with CF.2,33,39
Provision of Care for Adults with Cystic Fibrosis
The forecasted changes in demographics outlined previously will result in a significant burden on adult CF services over the next 20 years.2 This section will review the current guidelines for adult CF services and explore how these may be adopted and developed to deliver optimal care in coming years. It is critically important that CF teams and communities engage and discuss how high-quality CF care can be
delivered when resources for health care are constantly under pressure. There is good quality evidence from many treatments in CF that they are cost-effective, and it is important that CF research addresses the health economics of specialist care based on realistic high-quality evidence.40,41 Clinical trials and clinical research with strong health economic supporting data from real-world evidence, including registries, are of utmost importance to ensure that we are offering value-based health care in CF. CF is well placed to do this, thanks to high-fidelity CF registries with longitudinal data that allow complex analyses and bench- marking including between countries of care delivery.
Current guidelines emphasize the importance of MDT care for adults with CF based on medical leadership usually from a background in respiratory medicine. Care provision requires high-quality and usually hospital-based facilities (frequently associated with a medical school/university) for ambulatory and inpatient care that take into account the risk of cross infection and provide sufficient access for all MDT members.21,23 There should be a clear pathway for people with CF to access the care team at any time. Where possible health care programs for CF should have appropriate facilities to deliver treatment in the person’s home, particularly intravenous antibiotic therapy and additional treatments such as enteral feeding, oxygen therapy, and noninvasive ventilation.42,43 A CF center should also maintain local and national registries recording key information about individual people’s clinical condition and treatment, complications, and outcomes. This should also be used for patient care and quality improvement. Data in such registries should be available individually to the person with CF and may be used in the future to collect data from patient-reported outcomes and wearable devices that
assist in self-monitoring.44,45
The CF MDT should include a core team of adult physicians, specialist nurses, physiotherapists, dieticians, pharmacists, social workers, and clinical psychologists in proportion to the size of the adult CF center23,39,45 (►Table 1). Leadership of this team is usually by the adult respiratory physician, though there is no reason why with appropriate skills and training other MDT members may take such a role. This leadership role may be best rotated with colleagues every few years. Other specialist services are shown in ►Table 2.
These largely cover the nonrespiratory consequences of CFTR dysfunction. CF-related diabetes (CFRD) and liver disease are particularly problematic and should have designated special- ists who are integrated with the CF team.45–47 With increasing age, many conditions not previously associated with CF may also require support from other clinical disciplines. This emphasizes the importance of integration within a wider health care system to ensure specialist input from these other relevant disciplines. However, it remains critically important that the core MDT integrates advice and treatment pathways from different disciplines, as there is the potential for conflicts in the prioritization of management and drug interactions.45 Integrating care in this complex disease as the disease pro- gresses is increasingly challenging and requires the right balance of overall CF experience supported by high-quality multispecialist input for each patient.
Transition to Adult Care
Transition to adult care is best when planned early. A strong working partnership with pediatric care centers should be developed from the age of 13 to 14 with the adult center.48 A named practitioner from both children and adult services to manage the transition has been shown to be helpful, with strong collaboration with parents and the young adult who is making the transition.48,49 Where possible, parents should
also be helped in making this adjustment as it is important that the young person with CF is supported by them to take on more responsibility while maintaining a supportive role.
Transition does not finish when the individual moves to the adult service.48,50 There should be forward planning over the first few years following transfer to ensure that they are adapting to the adult service and as well as to support them as they transition in their lives from teenager to an indepen- dent adult.
Pulmonary Complications
People with CF develop a range of pulmonary complications including chronic infection with a range of bacteria, fungi, and viruses1,51 The potential for cross infection with Pseudomonas aeruginosa, Burkholderia cepacia complex, methicillin-resis- tant Staphylococcus aureus, and nontuberculous mycobacteria weighs heavily on people with CF and their care teams. Several guidelines have been published to reduce the potential for patient-to-patient cross infection and environmental infec- tion.52–54 CF centers should consider these guidelines in light of the institution’s infection control policies and the microbiological epidemiology of the center. Outbreaks with all of the a forementioned organisms have been described, and all cen- ters should have a surveillance program with molecular testing to identify new clusters of organisms as quickly as possible. A further problem with many of these bacteria and fungi is that they frequently demonstrate resistance to antibiotics due to a combination of intrinsic resistance and the effect of frequent antibiotic treatment.55–59
Chronic infection with bacteria, fungi, and viruses are also associated with recurrent pulmonary exacerbations, which cause a more rapid decline in lung function, impaired qualityof life, and reduced survival.60–63 Prevention of these events is a key priority in CF care, and this can be achieved by the optimization of mucoactive, antimicrobial, and CFTR modula- tor therapies, all of which have been shown to reduce the frequency of these events.1,63 When exacerbations occur, they should be treated according to the infecting organism/s for an appropriate length of time. These regimes have been reviewed elsewhere and excellent guidelines are also available.59,60,63
Maintaining a Multidisciplinary Team
Caring for people with CF is an intensely personal and emotionally demanding health care role. This is matched by the professional satisfaction of providing care over a period of time and in collaboration with the individual with CF, helping them make decisions, which enable them to pursue educational, career, lifestyle, and family aspira- tions. However, the progressive nature of the disease has significant impacts on those providing care. Maintaining the well-being and functional coherence of an MDT is of critical importance in ensuring the best care. Frequent opportunities for teams to discuss the more difficult aspects of CF care, such as reviewing all deaths, managing ACFLD and prolonged hospital admissions, and dealing with the challenges of adherence and concordance with treatment regimes, among many others, present personal and intrateam dilemmas, which require support and engagement across the MDT. It is also important for patients that consistent advice is provided, though this not should be at the expense of a dogmatic approach. All team members should be encouraged to contribute from their professional disciplinary area and also with their emotional intelligence and understanding particular individuals. MDT should be encouraged and sup- ported to look after their own well-being, with particular care to avoiding overworking, personalizing health care team/patient relationships, and avoiding dysfunctional behaviors that undermine others within the team.
Training of future MDTs is very important and should be a priority for the CF community.1,5,146 CF physicians with com- plementary backgrounds in infectious diseases, general internal medicine, and gastroenterology, are to be encouraged to participate and indeed, where appropriate, provideleadership, but adult CF teams are usually within the respiratory medicine community. To attract the next generation of clinicians in all disciplines, it is important that CF attracts trainees and early career practitioners grounded in respiratory medicine.146 Additional training in the GI, endocrine, and other disease- causing areas is required to provide a CF center with leader- ship. CF is now such a complex condition that specific training in medical, nursing, and allied health professional courses should be sought, particularly at the postgraduate level, to equip clinicians within the MDT for future care.
Conclusions
CF care is at a very exciting and challenging juncture. The growing number of adults which will increase with CFTR modulator drugs may result in less morbidity for some for a time, but this is likely to still result in an older patient community with complex disease.
Care for people with CF will require expertise in respiratory disease and an MDT for other organ systems and to deliver the complex treatment regimens required. This should be deliv- ered through a core MDT and a range of experts in other disease areas to support complications in other systems. The future care should aim to deliver as much of the required treatments in the community and to empower and enable people with CF to live, CTP-656 contributing to society and enjoying the normal aspirations of adults who do not have any disease.