LONG TERM MANAGEMENT OF CYSTIC FIBROSIS

Presse medicale (Paris, France : 1983), 2017

Cystic fibrosis (CF) is a complex multisystem disease with considerable between patient variability in its manifestations and severity. In the past several decades, the range of treatments and the evidence to support their use for the pulmonary and extrapulmonary manifestations of CF have increased dramatically, contributing to the improved median survival of patients. As therapy for CF has evolved, new challenges including treatment adherence, medication intolerance and allergy, medical complications and coping with the burden of disease in the context of having a family and managing employment have arisen. While the majority of current therapy focuses primarily on improving symptoms, new therapies (CFTR modulators) target the underlying genetic defect.

Journal of Pediatric Health Care, 1996

Therapeutic advances in respiratory disease, 2011

Cystic fibrosis (CF) is an autosomal recessive disorder that affects approximately 1 in 3,000 Caucasian births, or 30,000 individuals in the US and 70,000 worldwide. The discovery of the CF gene, isolation of the CFTR protein and understanding of molecular mechanisms behind the clinical expression of CF are being translated into newer treatments. Treatments for CF and its manifestations are discussed in this article including inhaled antibiotics, hydrator therapies, anti-inflammatory agents and protein modifiers. New and experimental treatments that are in development are also discussed. Outcomes for these treatments are forced expiratory volume in one second (FEV(1)) improvement, CF-related quality of life, use of intravenous antibiotics and frequency of exacerbations and hospitalizations.

Pediatric Pulmonology, 2012

Cystic fibrosis (CF) is a complex, chronic, multisystem disease for which there is currently no cure. Nonetheless, advances in management have led to dramatic improvements in patient survival. With this development, new issues have arisen for CF patients and their care providers, including an increased symptom burden and increased frequency of comorbidities as patients reach older ages, leading to the need for a highly complicated and timeconsuming regimen of treatments. Such high symptom and treatment burden often leads to non-adherence and low levels of competence with administration of therapy, both of which may have detrimental impacts on CF outcomes. Optimal management is also hindered by other patient-related factors, including inadequacies in disease education which may lead to issues with self-management. This is particularly important during the transition from parent-directed therapy to independent self-management that occurs during adolescence and early adulthood. Clinicians are also faced with a considerable challenge when selecting interventions for individual patients; although the paradigm of aggressive care necessitates a wide range of therapies, there is a limited evidence base with which to compare available therapeutic regimens. Novel pharmacological agents are being developed to target the underlying cause of CF, while non-pharmacological interventions aim to improve competence and maximize adherence and health outcomes. Comparative effectiveness research is needed to simplify management and facilitate the implementation of appropriate treatment strategies. Pediatr Pulmonol.

BMJ (Clinical research ed.), 2017

Cystic fibrosis is a life limiting autosomal recessive disorder that affects up to one in 2500 babies born in the UK. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator protein, which acts at the cell surface in all mucus producing organs in the body. It is a multisystem disorder, affecting the lungs, pancreas, liver, and intestine. It is usually diagnosed in the UK through a neonatal screening programme, although diagnosis can be made later, and even in adult life. 1 The median age at diagnosis is 2 months. 1 In the past, when early death was common, cystic fibrosis was uncommon in adults, but with improved management this is no longer the case in more developed countries. However, in low income countries, mortality in childhood is still high. 2 At present, more than 60% of people on the UK cystic fibrosis registry are aged over 16. 1 This article summarises the recent National Institute for Health and Care Excellence (NICE) guidance on the diagnosis and management of cystic fibrosis in children, young people, and adults. 3 This guideline was commissioned with the aim of improving the diagnosis and management of cystic fibrosis. It covers indications for referral, diagnosis, monitoring, and recognition of complications. It addresses the management of pulmonary disease, including infection in cystic fibrosis, and the prevention of cross infection. It also provides recommendations on service organisation, information, and support to people with cystic fibrosis, and where appropriate to parents and carers. Although the guideline recommends that the care of people with cystic fibrosis is provided by specialist cystic fibrosis centres, this summary is specifically aimed at non-specialist healthcare professionals, for example in primary care, who might become involved in the care of people with cystic fibrosis for a variety of reasons. Healthcare professionals might need to recognise complications of the condition (for example, fertility problems), or when to signpost on to other services.

2013

Cystic fibrosis (CF) is one of the most prevalent fatal autosomal recessive diseases in the United States. Although early diagnosis and improved treatment methods have helped increase the median predicted survival age of CF patients, CF remains a burdensome and life-threatening disease. Furthermore, the challenges of treating CF are amplified by the fact that there are over 1,800 known CF mutations. Recent advances in drug therapy have begun to target the main classes of CF mutations at the protein level, addressing mutational events instead of downstream disease processes. Three drugs, including ivacaftor, which has been approved by the United States Food and Drug Administration, and VX-809 and ataluren, which are still in clinical trial, have been shown to improve patient clinical measures. VX-809 targets the most prevalent CF mutation, F508del, and used in combination with ivacaftor was shown to significantly decrease mean sweat chloride concentrations and significantly increase ...

Journal of Translational Medicine, 2017

Objectives: Study of currently approved drugs and exploration of future clinical development pipeline therapeutics for cystic fibrosis, and possible limitations in their use. Methods: Extensive literature search using individual and a combination of key words related to cystic fibrosis therapeutics. Key findings: Cystic fibrosis is an autosomal recessive disorder due to mutations in CFTR gene leading to abnormality of chloride channels in mucus and sweat producing cells. Respiratory system and GIT are primarily involved but eventually multiple organs are affected leading to life threatening complications. Management requires drug therapy, extensive physiotherapy and nutritional support. Previously, the focus was on symptomatic improvement and complication prevention but recently the protein rectifiers are being studied which are claimed to correct underlying structural and functional abnormalities. Some improvement is observed by the corrector drugs. Other promising approaches are gene therapy, targeting of cellular interactomes, and newer drugs for symptomatic improvement. Conclusions: The treatment has a long way to go as most of the existing therapeutics is for older children. Other limiting factors include mutation class, genetic profile, drug interactions, adverse effects, and cost. Novel approaches like gene transfer/gene editing, disease modeling and search for alternative targets are warranted.

Expert Review of Respiratory Medicine, 2015

Clinical Pharmacology & Therapeutics, 2012

state art nature publishing group Cystic fibrosis, also referred as mucoviscidosis, is a lifethreatening autosomal recessive genetic disorder affecting multiple organs, most critically the respiratory and digestive systems. The prognosis for cystic fibrosis has significantly improved as a result of earlier diagnosis, better treatment, and expanded access to specialized care. Modern cystic fibrosis care incorporates a longitudinal strategy that includes early prenatal detection, management of disease manifestations during infancy and childhood, and chronic treatment in the adult. Decoding the pathogenesis of cystic fibrosis has advanced personalized treatment algorithms. Most notable is the realization that cystic fibrosis is a generalized exocrinopathy with reduced chloride ion transport across cell membranes as a consequence of a primary genetic disorder within the long arm of chromosome 7 encoding the transmembrane conductance regulating protein (CFTR). In healthy duct epithelia, chloride is transported by plasma membrane channels. Opening of chloride channels is mediated by an agonist-induced increase in cyclic adenosine monophosphate, followed by activation of protein kinase A, which phosphorylates channel proteins. 1 The impact of defective chloride transport differs in various tissues. In sweat gland ducts, it leads to decreased reabsorption of sodium chloride from the lumen, resulting in an increased concentration of sweat chloride, the basis for clinical diagnosis of cystic fibrosis. In other epithelia, especially the respiratory and intestinal epithelia, as well as in the biliary and pancreatic ducts, chloride channel defects result in loss or reduction of chloride secretion. Active sodium absorption is also increased, and these concomitant ionic changes increase water reabsorption from the lumen. As a consequence, dehydration of the mucus layer leads to viscid secretions, resulting in lumen obstruction and predisposing over time to recurrent infection, inflammation, fibrosis, and organ failure. The pronounced improvement in life expectancy for patients with cystic fibrosis, which is experienced across global health systems, particularly in developed countries, is a result of early diagnosis and improved symptomatic treatment based on control of airway infections, intestinal function, mobilization of secretions, reduction of inflammation, and improved nutrition. 2 Treating the fundamental defect underlying cystic fibrosis through a gene-modifying therapy offers the prospect of potential cures. In this regard, encouraging results from early clinical trials with mutation-correcting drug and gene therapy pave the way to more efficient management in the future. 3 Prenatal Diagnosis Cystic fibrosis is a hereditary, autosomal recessive disease, passed on from parents to offspring, with the highest prevalences of 1 in 3,000 Caucasian children of northern European descent and from North America and 1 in 2,300 in the Ashkenazi Jewish population. Other ethnic and racial groups are less commonly affected, reflected in the prevalences of 1 in 10,000 in the Latino American population and 1 in 15,000 in African Americans. The disease is uncommon in Africa and Asia, with reported frequencies ranging from 1 in 35,000 to 1 in 350,000. The earliest manifestation of cystic fibrosis may be associated with bowel lesions identified at prenatal ultrasonography, especially

International Journal of Molecular Sciences

Cystic fibrosis (CF) is the most common lethal genetic disease in Caucasian populations, occurring in approximately 1 in 3000 newborns worldwide [...]

Expert Opinion on Orphan Drugs, 2017

Introduction: Cystic Fibrosis (CF) is a disease caused by different class mutations in the CF transmembrane conductance regulator (CFTR) gene. It can therefore benefit from a personalized medicine approach based on the individual genotype of each patient. 2 Areas covered: This review provides a detailed overview of the current major development of new CF treatments that target the basic CF defect. The review summarizes gene therapy, mRNA repair strategies, read-through agents, and CFTRmodulators (potentiators, correctors, stabilizers, amplifiers and different combination therapies). Expert opinion: We are currently perhaps at the most exciting stage in the history of CF, with the potential to cure the disease now on the horizon. The good results obtained with ivacaftor in patients with at least one gating mutation having encouraged researchers to develop agents targeting the basic CF defect; such agents are designed for use as monotherapy or combination therapy in patients with other genotypes. However, disease aspects such as pharmacoeconomics, drug-drug interactions, use in infants, or the need for additional endpoints in future clinical trials, may ultimately hinder research and the potential availability of novel drugs for CF patients.

2016

The purpose of this review was to identify the history of and advances in cystic fibrosis (CF). New treatment plans, medication developments, and a historical perspective of airway clearance therapy (ACT) will be presented. The importance of treatment compliance and time management in the care of cystic fibrosis patients will also be discussed. Furthermore, the development of cystic fibrosis clinics and the pivotal role they play in the treatment of the disease will be addressed. Lastly, a brief discussion concerning the need for and process of lung transplantation will be reported.

Journal of the American Academy of Nurse Practitioners, 2012

Advances in pediatrics, 2008

In summary, there is a significant interplay between the pulmonary manifestations and nutritional status of CF patients. The advances in CF clinical care in the past 2 decades are mainly attributed to anti-infective therapy as well as aggressive nutritional management. Currently, there are multiple therapeutic agents that are in clinical trial that target either the underlying CFTR defect or the downstream effects of CFTR. The broad spectrum of therapeutic agents being studied as well as the advances in therapies that target the underlying CFTR defect are exciting, making it likely that at least one of the treatments will make a major difference in how we will treat CF in the future.