Title: The future of cystic fibrosis care: a global perspective
Abstract: The past six decades have seen remarkable improvements in health outcomes for people with cystic fibrosis, which was once a fatal disease of infants and young children. However, although life expectancy for people with cystic fibrosis has increased substantially, the disease continues to limit survival and quality of life, and results in a large burden of care for people with cystic fibrosis and their families. Furthermore, epidemiological studies in the past two decades have shown that cystic fibrosis occurs and is more frequent than was previously thought in populations of non-European descent, and the disease is now recognised in many regions of the world. The Lancet Respiratory Medicine Commission on the future of cystic fibrosis care was established at a time of great change in the clinical care of people with the disease, with a growing population of adult patients, widespread genetic testing supporting the diagnosis of cystic fibrosis, and the development of therapies targeting defects in the cystic fibrosis transmembrane conductance regulator (CFTR), which are likely to affect the natural trajectory of the disease. The aim of the Commission was to bring to the attention of patients, health-care professionals, researchers, funders, service providers, and policy makers the various challenges associated with the changing landscape of cystic fibrosis care and the opportunities available for progress, providing a blueprint for the future of cystic fibrosis care. The discovery of the CFTR gene in the late 1980s triggered a surge of basic research that enhanced understanding of the pathophysiology and the genotype–phenotype relationships of this clinically variable disease. Until recently, available treatments could only control symptoms and restrict the complications of cystic fibrosis, but advances in CFTR modulator therapies to address the basic defect of cystic fibrosis have been remarkable and the field is evolving rapidly. However, CFTR modulators approved for use to date are highly expensive, which has prompted questions about the affordability of new treatments and served to emphasise the considerable gap in health outcomes for patients with cystic fibrosis between high-income countries, and low-income and middle-income countries (LMICs). Advances in clinical care have been multifaceted and include earlier diagnosis through the implementation of newborn screening programmes, formalised airway clearance therapy, and reduced malnutrition through the use of effective pancreatic enzyme replacement and a high-energy, high-protein diet. Centre-based care has become the norm in high-income countries, allowing patients to benefit from the skills of expert members of multidisciplinary teams. Pharmacological interventions to address respiratory manifestations now include drugs that target airway mucus and airway surface liquid hydration, and antimicrobial therapies such as antibiotic eradication treatment in early-stage infections and protocols for maintenance therapy of chronic infections. Despite the recent breakthrough with CFTR modulators for cystic fibrosis, the development of novel mucolytic, anti-inflammatory, and anti-infective therapies is likely to remain important, especially for patients with more advanced stages of lung disease. As the median age of patients with cystic fibrosis increases, with a rapid increase in the population of adults living with the disease, complications of cystic fibrosis are becoming increasingly common. Steps need to be taken to ensure that enough highly qualified professionals are present in cystic fibrosis centres to meet the needs of ageing patients, and new technologies need to be adopted to support communication between patients and health-care providers. In considering the future of cystic fibrosis care, the Commission focused on five key areas, which are discussed in this report: the changing epidemiology of cystic fibrosis (section 1); future challenges of clinical care and its delivery (section 2); the building of cystic fibrosis care globally (section 3); novel therapeutics (section 4); and patient engagement (section 5). In panel 1, we summarise key messages of the Commission. The challenges faced by all stakeholders in building and developing cystic fibrosis care globally are substantial, but many opportunities exist for improved care and health outcomes for patients in countries with established cystic fibrosis care programmes, and in LMICs where integrated multidisciplinary care is not available and resources are lacking at present. A concerted effort is needed to ensure that all patients with cystic fibrosis have access to high-quality health care in the future. The past six decades have seen remarkable improvements in health outcomes for people with cystic fibrosis, which was once a fatal disease of infants and young children. However, although life expectancy for people with cystic fibrosis has increased substantially, the disease continues to limit survival and quality of life, and results in a large burden of care for people with cystic fibrosis and their families. Furthermore, epidemiological studies in the past two decades have shown that cystic fibrosis occurs and is more frequent than was previously thought in populations of non-European descent, and the disease is now recognised in many regions of the world. The Lancet Respiratory Medicine Commission on the future of cystic fibrosis care was established at a time of great change in the clinical care of people with the disease, with a growing population of adult patients, widespread genetic testing supporting the diagnosis of cystic fibrosis, and the development of therapies targeting defects in the cystic fibrosis transmembrane conductance regulator (CFTR), which are likely to affect the natural trajectory of the disease. The aim of the Commission was to bring to the attention of patients, health-care professionals, researchers, funders, service providers, and policy makers the various challenges associated with the changing landscape of cystic fibrosis care and the opportunities available for progress, providing a blueprint for the future of cystic fibrosis care. The discovery of the CFTR gene in the late 1980s triggered a surge of basic research that enhanced understanding of the pathophysiology and the genotype–phenotype relationships of this clinically variable disease. Until recently, available treatments could only control symptoms and restrict the complications of cystic fibrosis, but advances in CFTR modulator therapies to address the basic defect of cystic fibrosis have been remarkable and the field is evolving rapidly. However, CFTR modulators approved for use to date are highly expensive, which has prompted questions about the affordability of new treatments and served to emphasise the considerable gap in health outcomes for patients with cystic fibrosis between high-income countries, and low-income and middle-income countries (LMICs). Advances in clinical care have been multifaceted and include earlier diagnosis through the implementation of newborn screening programmes, formalised airway clearance therapy, and reduced malnutrition through the use of effective pancreatic enzyme replacement and a high-energy, high-protein diet. Centre-based care has become the norm in high-income countries, allowing patients to benefit from the skills of expert members of multidisciplinary teams. Pharmacological interventions to address respiratory manifestations now include drugs that target airway mucus and airway surface liquid hydration, and antimicrobial therapies such as antibiotic eradication treatment in early-stage infections and protocols for maintenance therapy of chronic infections. Despite the recent breakthrough with CFTR modulators for cystic fibrosis, the development of novel mucolytic, anti-inflammatory, and anti-infective therapies is likely to remain important, especially for patients with more advanced stages of lung disease. As the median age of patients with cystic fibrosis increases, with a rapid increase in the population of adults living with the disease, complications of cystic fibrosis are becoming increasingly common. Steps need to be taken to ensure that enough highly qualified professionals are present in cystic fibrosis centres to meet the needs of ageing patients, and new technologies need to be adopted to support communication between patients and health-care providers. In considering the future of cystic fibrosis care, the Commission focused on five key areas, which are discussed in this report: the changing epidemiology of cystic fibrosis (section 1); future challenges of clinical care and its delivery (section 2); the building of cystic fibrosis care globally (section 3); novel therapeutics (section 4); and patient engagement (section 5). In panel 1, we summarise key messages of the Commission. The challenges faced by all stakeholders in building and developing cystic fibrosis care globally are substantial, but many opportunities exist for improved care and health outcomes for patients in countries with established cystic fibrosis care programmes, and in LMICs where integrated multidisciplinary care is not available and resources are lacking at present. A concerted effort is needed to ensure that all patients with cystic fibrosis have access to high-quality health care in the future. A patient's experience of cystic fibrosis careCare for people with cystic fibrosis has changed dramatically over my lifetime. The introduction of Pulmyzone (dornase alfa) in the mid-1990s, when I was a teenager, saw my lung function improve so much that I was able to complete a 6-hour moonlight hike through Richmond park, in London, UK, when previously even the short walk to school had left me out of breath. Although that lung capacity was not maintainable, the treatment is no doubt part of the reason why I am still alive at the age of 38 years. Full-Text PDF Progress in understanding the molecular pathology and microbiology of cystic fibrosisSince the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, cystic fibrosis has become a paradigm for cutting-edge basic, translational, and clinical research, which has transformed a devastating disease of childhood to a chronic condition with a reasonable quality of life that can last for decades. Being a monogenic autosomal recessive trait, cystic fibrosis was one of the first inherited disorders for which the disease-causing lesions were resolved by reverse genetics and subsequent mutation scanning of the affected gene. Full-Text PDF Clinical care for cystic fibrosis: preparing for the future nowThe survival of people with cystic fibrosis has improved dramatically over the past 60 years, such that adult patients now outnumber paediatric patients in some countries.1,2 This improvement can be attributed largely to advances in the treatment of complications of cystic fibrosis, but new therapies that target the underlying cause of cystic fibrosis—the absence or impaired functioning of the cystic fibrosis transmembrane conductance regulator (CFTR) protein—promise to transform health outcomes for patients with the disease. Full-Text PDF Cystic fibrosis lung disease and bronchiectasisIn a Lancet Respiratory Medicine Commission report, experts in cystic fibrosis from 18 countries present their view of the future of cystic fibrosis care.1 The Commission is a landmark at a point in time when the demography and management of cystic fibrosis are changing rapidly. The Commission comprehensively addresses future uncertainties and challenges for the field, including those associated with the management of lung disease.1 Full-Text PDF Correction to Lancet Respir Med 2019; published online Sept 27. https://doi.org/10.1016/S2213-2600(19)30337-6Bell SC, Mall MA, Gutierrez H, et al. The future of cystic fibrosis care: a global perspective. Lancet Respir Med 2019; published online Sept 27. https://doi.org/10.1016/S2213-2600(19)30337-6 —In this Commission, the following reference was omitted: Stahl M, Wielpütz MO, Ricklefs I, et al. Preventive inhalation of hypertonic saline in infants with cystic fibrosis (PRESIS). A randomized, double-blind, controlled study. Am J Respir Crit Care Med 2019; 199: 1238–48. This reference should have been cited after relevant text regarding hypertonic saline and lung clearance index in infants with cystic fibrosis, and has now been cited as reference number 523. Full-Text PDF Cystic fibrosis in TurkeyWe read with great interest The Lancet Respiratory Medicine Commission by Scott Bell, Felix Ratjen, and colleagues,1 which gives a comprehensive global perspective on cystic fibrosis care. We were pleased to see that the Commission gave a special focus to cystic fibrosis care in Turkey. However, in the space available, the authors were able to provide only brief details of clinical care in the country and we would like to take the opportunity to provide further information. Full-Text PDF Early-life origins of respiratory diseases: a key to preventionThe theme selected for this year's European Respiratory Society (ERS) International Congress, which drew to a close on Sept 9, 2020, was the early-life origins of respiratory diseases. The programme included a range of presentations and discussions that highlighted the need for a better understanding of factors associated with lung function trajectories throughout life, including lung development and ageing, and with the onset and course of respiratory diseases. Multidisciplinary research efforts will be needed to translate new findings into strategies for personalised treatment and disease prevention. Full-Text PDF