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1.
Cystic fibrosis bone disease treatment: Current knowledge and future directions.
Putman, MS, Anabtawi, A, Le, T, Tangpricha, V, Sermet-Gaudelus, I
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2019;:S56-S65
Abstract
Bone disease is a frequent complication in adolescents and adults with cystic fibrosis (CF). Early detection and monitoring of bone mineral density and multidisciplinary preventive care are necessary from childhood through adolescence to minimize CF-related bone disease (CFBD) in adult CF patients. Approaches to optimizing bone health include ensuring adequate nutrition, particularly intake of calcium and vitamins D and K, addressing other secondary causes of low bone density such as hypogonadism, encouraging weight bearing exercise, and avoiding bone toxic medications. Of the currently available anti-resorptive or anabolic osteoporosis medications, only bisphosphonates have been studied in individuals with CF. Future studies are needed to better understand the optimal approach for managing CFBD.
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2.
[Diagnostic possibilities of modern biochemical study of sputum from patients with cystic fibrosis (literature review).].
Kozlov, AV, Gusyakova, OA, Ereshchenko, AA, Khaliulin, AV
Klinicheskaia laboratornaia diagnostika. 2019;(1):24-28
Abstract
The review presents the pathobiochemical and molecular mechanisms of sputum formation in patients with cystic fibrosis associated with the pathophysiological features of the disease. Statistical data on the prevalence of this pathology in the world and in the Russian Federation are presented. The mechanisms of sputum formation and disorders of the mucociliary apparatus, leading to the accumulation of viscous bronchopulmonary secret in cystic fibrosis, are considered. The principles of the relationship between the rheological properties of sputum and the formation of inflammation in the lungs with the addition of a concomitant specific microflora in the bronchopulmonary system in patients with cystic fibrosis are presented. Describes the opportunities for biochemical studies of sputum of patients with this pathology: determining the activity of enzymes (myeloperoxidase), the content of proteinase inhibitors (α2-macroglobulin and α1-antitrypsin) and proinflammatory cytokines (IL-8 and TNFa), concentrations of iron and ferriferous proteins (lactoferrin and ferritin), which makes biochemical studies of sputum available, non-invasive, quick and cost-effective method of diagnosis, which can be widely used as an auxiliary laboratory method and makes it possible to use these metabolites as diagnostic markers to assess the severity of inflammation and infection of the lower respiratory tract and predict the development of respiratory complications in patients with cystic fibrosis.
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3.
Hypoglycemia in cystic fibrosis: Prevalence, impact and treatment.
Moheet, A, Chan, CL, Granados, A, Ode, KL, Moran, A, Battezzati, A
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2019;:S19-S24
Abstract
Hypoglycemia is a common and feared complication of insulin therapy. As in type 1 and type 2 diabetes, people with cystic fibrosis related diabetes are also at risk for hypoglycemia related to insulin therapy. Spontaneous hypoglycemia is also common in patients with CF without diabetes, who are not on glucose lowering medications. Spontaneous hypoglycemia in CF may also occur during or after an oral glucose tolerance test. In this review, we will discuss the definition, epidemiology, pathophysiology and impact of hypoglycemia, with a focus on people with cystic fibrosis. We will also review strategies to manage and prevent hypoglycemia.
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4.
Vitamin D deficiency and its treatment in cystic fibrosis.
Daley, T, Hughan, K, Rayas, M, Kelly, A, Tangpricha, V
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2019;:S66-S73
Abstract
Vitamin D deficiency is a common finding in individuals with cystic fibrosis (CF), despite routine supplementation. Hypovitaminosis D is often the result of fat malabsorption, but other contributors include increased latitude, poor nutritional intake, decreased sun exposure, impaired hydroxylation of vitamin D, and non-adherence to the prescribed vitamin D regimen. Vitamin D is critical for calcium homeostasis and optimal skeletal health, and vitamin D deficiency in CF can lead to skeletal complications of osteopenia and osteoporosis. Over time, our understanding of treatment regimens for vitamin D deficiency in CF has evolved, leading to recommendations for higher doses of vitamin D to achieve target levels of circulating 25-hydroxyvitamin D. There is also some evidence that vitamin D deficiency may have non-skeletal consequences such as an increase in pulmonary exacerbations. The exact mechanisms involved in the non-skeletal complications of vitamin D deficiency are not clearly understood, but may involve the innate immune system. Future clinical studies are needed to help address whether vitamin D has a role in CF beyond skeletal health.
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5.
Anti-inflammatories and mucociliary clearance therapies in the age of CFTR modulators.
Perrem, L, Ratjen, F
Pediatric pulmonology. 2019;:S46-S55
Abstract
Cystic fibrosis (CF) is a genetic and life-limiting disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. This multi-system disease is characterized by progressive lung disease and pancreatic insufficiency amongst other manifestations. CFTR primarily functions as a chloride channel that transports ions across the apical membrane of epithelial cells but has other functions, including bicarbonate secretion and inhibition of sodium transport. Defective CFTR disrupts these functions, causing viscous and dehydrated mucus to accumulate, compromising the airway lumen and contributing to obstructive pulmonary disease. The combination of CFTR dysfunction, mucus obstruction, and infection drive an exaggerated and dysfunctional inflammatory response, which contributes to irreversible airway destruction and fibrosis. CFTR modulators, an exciting new class of drugs, increase the expression and/or function of CFTR variant protein and improve multiple clinical endpoints, such as lung function, pulmonary exacerbation rates, and nutritional status. However, these genotype-specific drugs are not universally available, the clinical response is variable, and lung function still declines over time when bronchiectasis is established. Consequently, even in the age of CFTR modulators, we must target other important aspects of the CF airway disease, such as inflammation and mucociliary clearance. This review highlights the mechanisms of inflammation and mucus accumulation in the CF lung and discusses anti-inflammatory and mucociliary clearance agents that are currently in development focusing on compounds for which clinical trial data have recently become available.
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6.
Vitamin K and cystic fibrosis: A gordian knot that deserves our attention.
Hatziparasides, G, Loukou, I, Moustaki, M, Douros, K
Respiratory medicine. 2019;:36-42
Abstract
Cystic fibrosis (CF) is an inherited genetic disorder with multiorgan involvement. Gastrointestinal tract dysfunction leads to fat and fat-soluble vitamins (A,D,E,K) malabsorption and deficiency of these vitamins. Subclinical vitamin K (VK) deficiency seems to be a common problem in CF patients. However, despite the rest of fat-soluble vitamins being routinely supplemented, this is not a universal clinical practice for VK. Inefficient levels of VK may have significant effects on blood coagulation and bone formation. There are also some data indicating that VK may play a key role on regulation of inflammation. Supplementing CF patients with VK seems rational, but the appropriate dosing regimens are still a matter of debate. This review will try to delineate the problem and communicate the latest opinions on this controversial issue.
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7.
Association Between Fat-Free Mass and Pulmonary Function in Patients With Cystic Fibrosis: A Narrative Review.
Gomes, A, Hutcheon, D, Ziegler, J
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2019;(5):715-727
Abstract
The association between body mass index (BMI) and pulmonary function in patients with cystic fibrosis (CF) is well established, yet BMI as the sole indicator of nutrition status fails to assess body composition, specifically fat-free mass (FFM). Reduced FFM is a characteristic of undernutrition and is associated with decreased pulmonary function. A critical review of the literature was undertaken to explore available evidence on the use of FFM derived from dual-energy X-ray absorptiometry (DXA), compared with BMI, to assess pulmonary function and thereby nutrition status in patients with CF. Four cross-sectional studies that met predefined inclusion and exclusion criteria were selected for review. Based on the evidence reviewed, reduced FFM was associated with reduced pulmonary function in both children and adults with CF. FFM was reduced among patients who may not otherwise be identified as at nutrition risk based on BMI alone. FFM, as compared with BMI, appears to be a better indicator of pulmonary function and nutrition status in patients with CF. Although future research is needed to identify and determine FFM measurements that are associated with improved pulmonary function and nutrition status in patients with CF, these findings highlight the potential value and clinical utility of using FFM measurements derived from DXA among patients with CF. Together, FFM and BMI may provide a more comprehensive picture of nutrition status during the nutrition assessment of the patient with CF.
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8.
Nutrition in cystic fibrosis: From the past to the present and into the future.
Altman, K, McDonald, CM, Michel, SH, Maguiness, K
Pediatric pulmonology. 2019;:S56-S73
Abstract
Nutritional management is an integral part of multidisciplinary care for persons with cystic fibrosis. This review will look at how nutrition care has evolved over time. In addition, we will look at how some newer therapies impact nutrition care.
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9.
Mucus, mucins, and cystic fibrosis.
Morrison, CB, Markovetz, MR, Ehre, C
Pediatric pulmonology. 2019;(Suppl 3):S84-S96
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Free full text
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Abstract
Cystic fibrosis (CF) is both the most common and most lethal genetic disease in the Caucasian population. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by the accumulation of thick, adherent mucus plaques in multiple organs, of which the lungs, gastrointestinal tract and pancreatic ducts are the most commonly affected. A similar pathogenesis cascade is observed in all of these organs: loss of CFTR function leads to altered ion transport, consisting of decreased chloride and bicarbonate secretion via the CFTR channel and increased sodium absorption via epithelial sodium channel upregulation. Mucosa exposed to changes in ionic concentrations sustain severe pathophysiological consequences. Altered mucus biophysical properties and weakened innate defense mechanisms ensue, furthering the progression of the disease. Mucins, the high-molecular-weight glycoproteins responsible for the viscoelastic properties of the mucus, play a key role in the disease but the actual mechanism of mucus accumulation is still undetermined. Multiple hypotheses regarding the impact of CFTR malfunction on mucus have been proposed and are reviewed here. (a) Dehydration increases mucin monomer entanglement, (b) defective Ca2+ chelation compromises mucin expansion, (c) ionic changes alter mucin interactions, and (d) reactive oxygen species increase mucin crosslinking. Although one biochemical change may dominate, it is likely that all of these mechanisms play some role in the progression of CF disease. This article discusses recent findings on the initial cause(s) of aberrant mucus properties in CF and examines therapeutic approaches aimed at correcting mucus properties.
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10.
Critical Care of the Adult Patient With Cystic Fibrosis.
King, CS, Brown, AW, Aryal, S, Ahmad, K, Donaldson, S
Chest. 2019;(1):202-214
Abstract
Cystic fibrosis (CF) is a multiorgan, genetic disease resulting from dysfunction of the CF transmembrane conductance regulator. The primary clinical manifestations are bronchiectasis, chronic pulmonary infections with recurrent exacerbations, and pancreatic insufficiency. Advances in CF care have led to improved survival, with more than one-half of those affected being adults. As a result, adult pulmonary and critical care physicians increasingly will be involved in the care of these patients. Patients with CF are at risk for numerous conditions that require ICU admission, including respiratory failure, massive hemoptysis, pneumothorax, hepatic failure, and bowel obstruction. Multiple aspects of the care of patients with CF benefit from specialized knowledge, including pancreatic enzyme replacement and nutritional support; airway clearance modalities; treatment of multiply resistant, polymicrobial infections, and unique drug metabolism. In extreme cases, patients may benefit from advanced therapies, including extracorporeal support and organ transplant. Optimal care of patients with CF requires a multidisciplinary care team that includes respiratory therapists, dieticians, social workers, psychologists, pharmacists, and physicians who have expertise in the treatment of this complex, multisystem disorder.