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Bergagnini-Kolev MC, Hsu S, Aitken ML, Goss CH, Hoofnagle AN, Zelnick LR, Lum D, Best CM, Thummel KE, Kestenbaum BR, de Boer IH, Lin YS. Metabolism and pharmacokinetics of vitamin D in patients with cystic fibrosis. J Steroid Biochem Mol Biol 2023; 232:106332. [PMID: 37217104 PMCID: PMC10524963 DOI: 10.1016/j.jsbmb.2023.106332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 05/15/2023] [Accepted: 05/19/2023] [Indexed: 05/24/2023]
Abstract
Patients with cystic fibrosis (CF) commonly have lower circulating concentrations of 25-hydroxyvitamin D (25(OH)D) than healthy populations. We comprehensively compared measures of vitamin D metabolism among individuals with CF and healthy control subjects. In a cross-sectional study, serum from participants with CF (N = 83) and frequency-matched healthy control subjects by age and race (N = 82) were analyzed for: 25(OH)D2 and 25(OH)D3, 1α,25-dihydroxyvitamins D2 and D3 (1α,25(OH)2D2 and 1α,25(OH)2D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), 4β,25-dihydroxyvitamin D3 (4β,25(OH)2D3), 25-hydroxyvitamin D3-3-sulfate (25(OH)D3-S), and 25-hydroxyvitamin D3-3-glucuronide (25(OH)D3-G). In a 56-day prospective pharmacokinetic study, ∼25 μg deuterium-labeled 25(OH)D3 (d6-25(OH)D3) was administered intravenously to participants (N = 5 with CF, N = 5 control subjects). Serum was analyzed for d6-25(OH)D3 and d6-24,25(OH)2D3, and pharmacokinetic parameters were estimated. In the cross-sectional study, participants with CF had similar mean (SD) total 25(OH)D concentrations as control subjects (26.7 [12.3] vs. 27.7 [9.9] ng/mL) and had higher vitamin D supplement use (53% vs. 22%). However, participants with CF had lower total 1α,25(OH)2D (43.6 [12.7] vs. 50.7 [13.0] pg/mL), 4β,25(OH)2D3 (52.1 [38.9] vs. 79.9 [60.2] pg/mL), and 25(OH)D3-S (17.7 [11.6] vs. 30.1 [12.3] ng/mL) (p < 0.001 for all). The pharmacokinetics of d6-25(OH)D3 and d6-24,25(OH)D3 did not differ between groups. In summary, although 25(OH)D concentrations were comparable, participants with CF had lower 1α,25(OH)2D, 4β,25(OH)2D3, and 25(OH)D3-S concentrations than healthy controls. Neither 25(OH)D3 clearance, nor formation of 24,25(OH)2D3, appears to account for these differences and alternative mechanisms for low 25(OH)D in CF (i.e., decreased formation, altered enterohepatic recirculation) should be explored.
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Affiliation(s)
| | - Simon Hsu
- Kidney Research Institute, University of Washington, Seattle, WA 98104, USA; Division of Nephrology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA.
| | - Moira L Aitken
- Division of Pulmonary, Critical Care and Sleep Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Christopher H Goss
- Department of Pediatrics, School of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Andrew N Hoofnagle
- Kidney Research Institute, University of Washington, Seattle, WA 98104, USA; Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Leila R Zelnick
- Kidney Research Institute, University of Washington, Seattle, WA 98104, USA; Division of Nephrology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Dawn Lum
- Kidney Research Institute, University of Washington, Seattle, WA 98104, USA; Division of Nephrology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Cora M Best
- Kidney Research Institute, University of Washington, Seattle, WA 98104, USA; Department of Laboratory Medicine and Pathology, School of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Kenneth E Thummel
- Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA
| | - Bryan R Kestenbaum
- Kidney Research Institute, University of Washington, Seattle, WA 98104, USA; Division of Nephrology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Ian H de Boer
- Kidney Research Institute, University of Washington, Seattle, WA 98104, USA; Division of Nephrology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Yvonne S Lin
- Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA
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Iniesta RR, Cook S, Oversby G, Koufaki P, Van der Linden ML, Vlachopoulos D, Williams CA, Urquhart DS. Systematic review and meta-analysis: Associations of vitamin D with pulmonary function in children and young people with cystic fibrosis. Clin Nutr ESPEN 2023; 54:349-373. [PMID: 36963882 DOI: 10.1016/j.clnesp.2023.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 01/17/2023] [Accepted: 02/06/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND Increasing evidence suggests that vitamin D is associated with pulmonary health, which may benefit children and young people diagnosed with Cystic Fibrosis (cypCF). Therefore, the aim of this systematic review was to evaluate primary research to establish associations between 25OHD and pulmonary health in cypCF. METHODS Electronic databases were searched with keywords related to CF, vitamin D, children/young people and pulmonary function. Included studies were cypCF (aged ≤21 years) treated in a paediatric setting. The primary outcome was lung function [forced expiratory volume in 1 s (FEV1% predicted)] and secondary outcomes were rate of pulmonary exacerbations, 25OHD status and growth. Evidence was appraised for risk of bias using the CASP tool, and quality using the EPHPP tool. A Meta-analysis was performed. RESULTS Twenty-one studies were included with mixed quality ratings and heterogeneity of reported outcomes. The Meta-analysis including 5 studies showed a significantly higher FEV1% predicted in the 25OHD sufficiency compared to the deficiency group [FEV1% predicted mean difference (95% CI) was 7.71 (1.69-13.74) %; p = 0.01]. The mean ± SD FEV1% predicted for the sufficient (≥75 nmol/L) vs. deficient (<50 nmol/L) group was 94.7 ± 31.9% vs. 86.9 ± 13.2%; I2 = 0%; χ2 = 0.5; df = 4). Five studies (5/21) found significantly higher rate of pulmonary exacerbations in those who were 25OHD deficient when compared to the sufficient group and negative associations between 25OHD and FEV% predicted. The effects of vitamin D supplementation dosages on 25OHD status (10/21) varied across studies and no study (12/21) showed associations between 25OHD concentration and growth. CONCLUSION This systematic review suggests that 25OHD concentration is positively associated with lung function and a concentration of >75 nmol/L is associated with reduced frequency of pulmonary exacerbations, which may slow lung function decline in cypCF. Future randomised clinical trials and mechanistic studies are warranted.
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Affiliation(s)
- Raquel Revuelta Iniesta
- Children's Health and Exercise Research Centre, Sport and Health Sciences, University of Exeter, Exeter, United Kingdom; Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom.
| | - Seren Cook
- Children's Health and Exercise Research Centre, Sport and Health Sciences, University of Exeter, Exeter, United Kingdom
| | - Gemma Oversby
- Centre for Health, Activity and Rehabilitation Research, Queen Margaret University, Edinburgh, United Kingdom
| | - Pelagia Koufaki
- Centre for Health, Activity and Rehabilitation Research, Queen Margaret University, Edinburgh, United Kingdom
| | - Marietta L Van der Linden
- Centre for Health, Activity and Rehabilitation Research, Queen Margaret University, Edinburgh, United Kingdom
| | - Dimitris Vlachopoulos
- Children's Health and Exercise Research Centre, Sport and Health Sciences, University of Exeter, Exeter, United Kingdom
| | - Craig A Williams
- Children's Health and Exercise Research Centre, Sport and Health Sciences, University of Exeter, Exeter, United Kingdom
| | - Don S Urquhart
- Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom; Department of Paediatric Respiratory and Sleep Medicine, Royal Hospital for Children and Young People, Edinburgh, United Kingdom
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Wysocka-Wojakiewicz P, Woś H, Wielkoszyński T, Pyziak-Skupień A, Grzybowska-Chlebowczyk U. Vitamin Status in Children with Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutation. Nutrients 2022; 14:nu14214661. [PMID: 36364923 PMCID: PMC9654413 DOI: 10.3390/nu14214661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/21/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022] Open
Abstract
Background: The issue of vitamin metabolism in children with cystic fibrosis screen positive, inconclusive diagnosis (CFSPID) is not well known. The aim of this study was to determine the status of vitamins A, D, E, and C in the blood of a group of children with CFSPID. Material and Methods: A total of 89 children were enrolled in the study (Me: 3.6 years, 52.8% boys), as follows: 28 with CFSPID, 31 with CF (cystic fibrosis), and 30 HC (healthy children). Their blood concentrations of vitamins A, D, E, and C, and their dietary intake of these vitamins were analysed in the study groups on the basis of a three-day food diary. Results: The patients with CFSPID had significantly higher serum vitamin D (p = 0.01) and E (p = 0.04) concentrations, compared to the children with CF. None of the children with CFSPID revealed vitamin A or E deficiencies. Patients with CF had been consuming significantly higher vitamin D and E amounts (p = 0.01). The vitamin concentrations did not depend either on the pancreatic/liver function or on anthropometric parameters. In total, 32.14% of patients with CF did not cover the baseline recommended calorie intake, and 53.6% and 36% did not take the recommended vitamin E and vitamin A intake, respectively. Conclusion: Children with CF and CFSPID did not fully cover the dietary recommendations for vitamin supply, but vitamin deficiency was found only in CF.
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Affiliation(s)
- Paulina Wysocka-Wojakiewicz
- Department of Pediatrics, Faculty of Medical Sciences, Medical University of Silesia, 40-752 Katowice, Poland
- Correspondence:
| | - Halina Woś
- Faculty of Health Sciences, University of Bielsko-Biala, 43-309 Bielsko-Biała, Poland
| | - Tomasz Wielkoszyński
- Higher School of Strategic Planning and Laboratory Medicine Centre, 41-303 Dąbrowa Górnicza, Poland
| | - Aleksandra Pyziak-Skupień
- Department of Children’s Diabetology, Silesian Medical University in Katowice, 40-752 Katowice, Poland
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Oliveira MS, Matsunaga NY, Rodrigues MLE, Morcillo AM, de Oliveira Ribeiro MAG, Ribeiro AF, de Fátima C P Servidoni M, Nogueira RJN, Pereira MC, Ribeiro JD, Toro AADC. Lung disease and vitamin D levels in cystic fibrosis infants and preschoolers. Pediatr Pulmonol 2019; 54:563-574. [PMID: 30663283 DOI: 10.1002/ppul.24260] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 01/03/2019] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Vitamin D acts on the immune system and lung response. Patients with cystic fibrosis (CF) may be deficient in this vitamin. The aims of the study were to evaluate vitamin D levels and severity of lung disease in infants and preschoolers diagnosed with CF, and to compare them to a group of children without pancreatic insufficiency (PI). METHODS Patients with CF up to 4 years old were included, and compared to an age-matched group of children without diagnosis of CF. CF group had medical records and High Resolution Thorax Computed Tomography (HRCCT) evaluated in order to verify the severity of lung disease. Information on demographic data, sun exposure habits, supplemental vitamin D therapy, and on the season at the time of vitamin D sampling were collected for both groups. RESULTS This study included 45 patients in the CF group and 102 in the non-CF group, with no differences in age (P = 0.327) between them. There was no association between vitamin D levels and markers of lung disease in the CF group. The non-CF group had lower daily sun exposure (P = 0.034), and lower supplementation than the CF group (P < 0.001). Supplementation and seasonality were the determinant variables for vitamin D levels, which were lower for non-supplemented children and for assessments during fall/winter. CONCLUSION There was no association between lung disease severity and vitamin D levels in CF group. Supplementation and seasonality were associated to higher vitamin levels.
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Affiliation(s)
- Marina S Oliveira
- School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
| | - Natasha Y Matsunaga
- School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
| | | | - André M Morcillo
- School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
| | | | - Antônio F Ribeiro
- School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
| | | | | | | | - José Dirceu Ribeiro
- School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
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Vitamin D intake, serum 25-hydroxy vitamin D and pulmonary function in paediatric patients with cystic fibrosis: a longitudinal approach. Br J Nutr 2018; 121:195-201. [DOI: 10.1017/s0007114518003021] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
AbstractPancreatic-insufficient children with cystic fibrosis (CF) receive age-group-specific vitamin D supplementation according to international CF nutritional guidelines. The potential advantageous immunomodulatory effect of serum 25-hydroxy vitamin D (25(OH)D) on pulmonary function (PF) is yet to be established and is complicated by CF-related vitamin D malabsorption. We aimed to assess whether current recommendations are optimal for preventing deficiencies and whether higher serum 25(OH)D levels have long-term beneficial effects on PF. We examined the longitudinal relationship between vitamin D intake, serum 25(OH)D and PF in 190 CF children during a 4-year follow-up period. We found a significant relationship between total vitamin D intake and serum 25(OH)D (β = 0·02; 95 % CI 0·01, 0·03; P = 0·000). However, serum 25(OH)D decreased with increasing body weight (β = –0·79; 95 % CI –1·28, –0·29; P = 0·002). Furthermore, we observed a significant relationship between serum 25(OH)D and forced expiratory volume in 1 s (β = 0·056; 95 % CI 0·01, 0·102; P = 0·018) and forced vital capacity (β = 0·045; 95 % CI 0·008, 0·082; P = 0·017). In the present large study sample, vitamin D intake is associated with serum 25(OH)D levels, and adequate serum 25(OH)D levels may contribute to the preservation of PF in children with CF. Furthermore, to maintain adequate levels of serum 25(OH)D, vitamin D supplementation should increase with increasing body weight. Adjustments of the international CF nutritional guidelines, in which vitamin D supplementation increases with increasing weight, should be considered.
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Ongaratto R, Rosa KMD, Eloi JC, Epifanio M, Marostica P, Pinto LA. Association between hypovitaminosis D and frequency of pulmonary exacerbations in children and adolescents with cystic fibrosis. ACTA ACUST UNITED AC 2018; 16:eAO4143. [PMID: 29694616 PMCID: PMC6063747 DOI: 10.1590/s1679-45082018ao4143] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 10/26/2017] [Indexed: 12/18/2022]
Abstract
Objective We evaluated the association between vitamin D levels and nutritional status, pulmonary function and pulmonary exacerbations in children and adolescents with cystic fibrosis. Methods 25-hydroxyvitamin D (25(OH)D) levels of 37 children and adolescents were retrospectively evaluated. Pulmonary function, body mass index, height for age, and pulmonary exacerbations episodes were associated with vitamin D levels divided into two groups: sufficient (≥30ng/mL) and hypovitaminosis (<30ng/mL). Results Hypovitaminosis D (25(OH)D <30ng/mL) was observed in 54% of subjects. The mean level of 25(OH)D was 30.53±12.14ng/mL. Pulmonary function and nutritional status were not associated with vitamin D levels. Pulmonary exacerbations over a 2-year period (p=0.007) and the period from measurement up to the end of the follow-up period (p=0.002) were significantly associated with vitamin D levels. Conclusion Hypovitaminosis D was associated with higher rates of pulmonary exacerbations in this sample of children and adolescents with cystic fibrosis. Hypovitaminosis D should be further studied as a marker of disease severity in cystic fibrosis. Further prospective and randomized studies are necessary to investigate causality of this association.
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Affiliation(s)
- Renata Ongaratto
- Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | | | - Juliana Cristina Eloi
- Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Matias Epifanio
- Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Paulo Marostica
- Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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Moustaki M, Loukou I, Priftis KN, Douros K. Role of vitamin D in cystic fibrosis and non-cystic fibrosis bronchiectasis. World J Clin Pediatr 2017; 6:132-142. [PMID: 28828295 PMCID: PMC5547424 DOI: 10.5409/wjcp.v6.i3.132] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 02/27/2017] [Accepted: 06/13/2017] [Indexed: 02/06/2023] Open
Abstract
Bronchiectasis is usually classified as cystic fibrosis (CF) related or CF unrelated (non-CF); the latter is not considered an orphan disease any more, even in developed countries. Irrespective of the underlying etiology, bronchiectasis is the result of interaction between host, pathogens, and environment. Vitamin D is known to be involved in a wide spectrum of significant immunomodulatory effects such as down-regulation of pro-inflammatory cytokines and chemokines. Respiratory epithelial cells constitutively express 1α-hydroxylase leading to the local transformation of the inactive 25(OH)-vitamin D to the active 1,25(OH)2-vitamin D. The latter through its autocrine and paracrine functions up-regulates vitamin D dependent genes with important consequences in the local immunity of lungs. Despite the scarcity of direct evidence on the involvement of vitamin D deficiency states in the development of bronchiectasis in either CF or non-CF patients, it is reasonable to postulate that vitamin D may play some role in the pathogenesis of lung diseases and especially bronchiectasis. The potential contribution of vitamin D deficiency in the process of bronchiectasis is of particular clinical importance, taking into consideration the increasing prevalence of vitamin D deficiency worldwide and the significant morbidity of bronchiectasis. Given the well-established association of vitamin D deficiency with increased inflammation, and the indicative evidence for harmful consequences in lungs, it is intriguing to speculate that the administration of vitamin D supplementation could be a reasonable and cost effective supplementary therapeutic approach for children with non-CF bronchiectasis. Regarding CF patients, maybe in the future as more data become available, we have to re-evaluate our policy on the most appropriate dosage scheme for vitamin D.
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Sands D, Mielus M, Umławska W, Lipowicz A, Oralewska B, Walkowiak J. Evaluation of factors related to bone disease in Polish children and adolescents with cystic fibrosis. Adv Med Sci 2015; 60:315-20. [PMID: 26183540 DOI: 10.1016/j.advms.2015.05.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 04/28/2015] [Accepted: 05/20/2015] [Indexed: 11/29/2022]
Abstract
PURPOSE The aim of the study was to evaluate factors related to bone formation and resorption in Polish children and adolescents with cystic fibrosis and to examine the effect of nutritional status, biochemical parameters and clinical status on bone mineral density. MATERIALS AND METHODS The study group consisted of 100 children and adolescents with cystic fibrosis with a mean age 13.4 years old. Anthropometric measurements, included body height, body mass and body mass index (BMI); bone mineral densitometry and biochemical testing were performed. Bone mineral density was measured using a dual-energy X-ray absorption densitometer. Biochemical tests included serum calcium, phosphorus, parathyroid hormone and vitamin D concentrations, as well as 24-h urine calcium and phosphorus excretion. Pulmonary function was evaluated using FEV1%, and clinical status was estimated using the Shwachman-Kulczycki score. RESULTS Standardized body height, body mass and BMI were significantly lower than in the reference population. Mean serum vitamin D concentration was decreased. Pulmonary disease was generally mild, with a mean FEV1% of 81%. Multivariate linear regression revealed that the only factors that had a significant effect on bone marrow density were BMI and FEV1%. There were no significant correlations between bone mineral density and the results of any of the biochemical tests performed. CONCLUSIONS Nutritional status and bone mineral density were significantly decreased in children and adolescents with cystic fibrosis. In spite of abnormalities in biochemical testing, the factors that were found to have the strongest effect on bone mineral density were standardized BMI and clinical status.
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Affiliation(s)
- Dorota Sands
- Cystic Fibrosis Centre, Institute of Mother and Child, Warsaw, Poland.
| | - Monika Mielus
- Cystic Fibrosis Centre, Institute of Mother and Child, Warsaw, Poland
| | | | - Anna Lipowicz
- Unit of Anthropology, Polish Academy of Sciences, Wrocław, Poland
| | - Beata Oralewska
- Department of Gastroenterology, Hepatology and Feeding Disorders Children's Health Memorial Institute, Warsaw, Poland
| | - Jarosław Walkowiak
- Department of Pediatric Gastroenterology & Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland
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Lindkvist B, Phillips ME, Domínguez-Muñoz JE. Clinical, anthropometric and laboratory nutritional markers of pancreatic exocrine insufficiency: Prevalence and diagnostic use. Pancreatology 2015; 15:589-97. [PMID: 26243045 DOI: 10.1016/j.pan.2015.07.001] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 07/06/2015] [Accepted: 07/07/2015] [Indexed: 12/11/2022]
Abstract
Pancreatic exocrine insufficiency (PEI) frequently occurs secondary to exocrine pancreatic disease (e.g. chronic pancreatitis, cystic fibrosis, cancer) or pancreatic/gastrointestinal surgery, resulting in the maldigestion of nutrients and consequently malnutrition. Pancreatic enzyme replacement therapy (PERT) is the cornerstone of PEI management. Despite its clinical relevance, the diagnosis of PEI in clinical practice is challenging, as the current gold standard test is cumbersome, and alternatives have limited availability or accuracy. There is a need for accurate and easily applicable diagnostic modalities. We review the prevalence of clinical symptoms and changes in anthropometric measurements and laboratory nutritional markers indicative of malnutrition in patients with PEI, and the relevance of these findings in diagnosing PEI and monitoring PERT efficacy. Based on limited available evidence, assessment of clinical symptoms, body weight, body mass index and other anthropometric parameters are not sensitive methods for PEI diagnosis, owing to high variability and multiple confounding factors, but appear useful in monitoring PERT efficacy. Limited evidence precludes strong recommendations but suggests that serum levels of vitamin E, magnesium, and plasma proteins, notably retinol binding protein, albumin, and prealbumin, may have diagnostic utility in PEI. Studies show that assessment of changes in these and other nutritional parameters is helpful in monitoring PERT efficacy. Further research is needed to confirm the diagnostic accuracy of these parameters for PEI. Until such data are available, a nutritional evaluation including circulating vitamin E, magnesium, retinol binding protein, albumin, and prealbumin may be used to evaluate the probability of PEI in clinical practice when reliable pancreatic function tests are not available.
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Affiliation(s)
- Björn Lindkvist
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Mary E Phillips
- Department of Nutrition and Dietetics, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK
| | - J Enrique Domínguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
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Li L, Somerset S. Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations. Clin Nutr 2015; 35:775-82. [PMID: 26159903 DOI: 10.1016/j.clnu.2015.06.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Revised: 05/25/2015] [Accepted: 06/12/2015] [Indexed: 01/29/2023]
Abstract
An increased prevalence of cystic fibrosis (CF) related complications such as impaired bone health and diabetes has accompanied increased survival of patients with CF. This review was conducted to determine the extent to which adults with CF are meeting current nutrition recommendations for micronutrients in association with CF-related complications management. Although dietary intake and nutritional status in CF has improved significantly in recent decades, micronutrient status seems to have diverged. While vitamin A and E intakes appear adequate, frequent vitamin D and K deficiency/insufficiency and compromised bone health in CF, occurs despite supplementation. Although deficiency of water-soluble vitamins and minerals is uncommon, ongoing surveillance will enhance overall health outcomes, particularly in cases of CF-related liver disease and deteriorated lung function and bone health. Salt and fluid status in CF may also need attention due to diminished thirst sensation and voluntary rehydration. Further investigation in micronutrient status optimisation in CF will inform the development of more effective and targeted nutrition therapies to enable integration of more refined recommendations for micronutrient intakes in CF based on individual needs and disease progression.
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Affiliation(s)
- Li Li
- School of Medicine, Griffith Health Institute, Griffith University, Brisbane, Queensland, Australia
| | - Shawn Somerset
- School of Medicine, Griffith Health Institute, Griffith University, Brisbane, Queensland, Australia; School of Allied Health, Faculty of Health Sciences, Australian Catholic University, Brisbane, Queensland, Australia.
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Norton L, Page S, Sheehan M, Mazurak V, Brunet-Wood K, Larsen B. Prevalence of Inadequate Vitamin D Status and Associated Factors in Children With Cystic Fibrosis. Nutr Clin Pract 2014; 30:111-6. [DOI: 10.1177/0884533614562839] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Laura Norton
- Faculty of Agriculture, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
- Alberta Health Services, Edmonton, Alberta, Canada
| | - Sarah Page
- Faculty of Agriculture, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
- Alberta Health Services, Edmonton, Alberta, Canada
| | | | - Vera Mazurak
- Faculty of Agriculture, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada
| | | | - Bodil Larsen
- Alberta Health Services, Edmonton, Alberta, Canada
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Vitamin D deficiency is associated with pulmonary exacerbations in children with cystic fibrosis. Ann Am Thorac Soc 2014; 11:198-204. [PMID: 24083951 DOI: 10.1513/annalsats.201208-068oc] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
RATIONALE Recent literature suggests vitamin D has an effect on lung function and on the lung's ability to fight infection, both important in the cystic fibrosis (CF) population as predictors of morbidity and mortality. OBJECTIVES Our study assessed associations between vitamin D and % predicted lung function, pulmonary exacerbations, and first Pseudomonas aeruginosa infection in children with CF. We hypothesized that children with CF who have 25-hydroxy vitamin D (25-OHD) levels less than 30 μg/L would have lower % predicted lung function and more pulmonary exacerbations than those with 25-OHD greater than or equal to 30 μg/L. METHODS This retrospective longitudinal study of 130 children aged 6 to 18 years between 2000 and 2012 examined 25-OHD levels classed in three vitamin D groups: sufficient (≥30 μg/L), insufficient (20-29 μg/L), and deficient (<20 μg/L). Longitudinal models followed individuals' changing vitamin D groups over time to compare numbers of pulmonary exacerbations (defined by hospitalization), incidence of first P. aeruginosa infection, and % predicted lung function. Cross-sectional comparisons between vitamin D groups were performed at ages 8, 12, and 16 years. MEASUREMENTS AND MAIN RESULTS The prevalence of vitamin D deficiency and insufficiency increased slowly through adolescence. The rate of exacerbations for the deficient vitamin D group, aged 15 to 18 years, was 13.1 per 10 patient-years, significantly higher than 4.3 per 10 patient-years for the insufficient and sufficient vitamin D groups (P < 0.05), which were not significantly different There were no differences between vitamin D groups in pulmonary function or incidence of first P. aeruginosa infection, which was about 2 per 10 patient-years. CONCLUSIONS Higher 25-OHD levels in children with CF were associated with lower rates of pulmonary exacerbations and, in adolescents, higher FEV1.
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Herscovitch K, Dauletbaev N, Lands LC. Vitamin D as an anti-microbial and anti-inflammatory therapy for Cystic Fibrosis. Paediatr Respir Rev 2014; 15:154-62. [PMID: 24332502 DOI: 10.1016/j.prrv.2013.11.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Cystic fibrosis (CF) is characterized by chronic infection and inflammation in the airways that lead to progressive lung damage and early death. Current anti-inflammatory therapies are limited by extensive adverse effects or insufficient efficacy. There is a large body of studies indicating beneficial anti-microbial and anti-inflammatory properties of vitamin D. Since most patients with CF present with vitamin D deficiency, and serum vitamin D levels demonstrate a positive correlation with lung function and negative correlation with airway inflammation and infection, correcting vitamin D deficiency may be an attractive therapeutic strategy in CF. The function of vitamin D is intricately tied to its metabolism, which may be impaired at multiple steps in patients with CF, with a potential to limit the efficacy of vitamin D supplementation. It is likely that the aforementioned beneficial properties of vitamin D require supplementation with doses of vitamin D markedly higher than those recommended to maintain proper bone function. This review will illustrate the potential for supplementation with vitamin D or its metabolites to modulate inflammation and improve defence against chronic infection in CF lung, as well as appropriate vitamin D supplementation strategies for improving lung function in CF.
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Affiliation(s)
- K Herscovitch
- Research Institute of McGill University Health Centre, Montreal, Quebec, Canada
| | - N Dauletbaev
- Research Institute of McGill University Health Centre, Montreal, Quebec, Canada
| | - Larry C Lands
- Research Institute of McGill University Health Centre, Montreal, Quebec, Canada; Division of Pediatric Respiratory Medicine, Department of Pediatrics, Montreal Children's Hospital-McGill University Health Centre.
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Bertolaso C, Groleau V, Schall JI, Maqbool A, Mascarenhas M, Latham N, Dougherty KA, Stallings VA. Fat-soluble vitamins in cystic fibrosis and pancreatic insufficiency: efficacy of a nutrition intervention. J Pediatr Gastroenterol Nutr 2014; 58:443-8. [PMID: 24345827 PMCID: PMC4212898 DOI: 10.1097/mpg.0000000000000272] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The aim of the study was to assess the impact of LYM-X-SORB (LXS), an organized lipid matrix that has been shown to be absorbable without pancreatic enzyme therapy on fat-soluble vitamin status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI). METHODS Children with CF and PI were randomized to daily LXS or an isocaloric placebo comparison supplement for 12 months. Serum vitamins A (retinol), D (25-hydroxyvitamin D[25D]), E (α-tocopherol, α-tocopherol:cholesterol ratio), and K (percentage of undercarboxylated osteocalcin [%ucOC] and plasma proteins induced by vitamin K absence factor II [PIVKA II]) were assessed at baseline and 12 months. Dietary intake was determined using 3-day weighed food records and supplemental vitamin intake by a comprehensive questionnaire. RESULTS A total of 58 subjects (32 boys, age 10.3 ± 2.9 years [mean ± standard deviation]) with complete serum vitamin, dietary and supplemental vitamin data were analyzed. After adjusting for dietary and supplemental vitamin intake, serum retinol increased 3.0 ± 1.4 μg/dL (coefficient ± standard error) (adjusted R2 = 0.02, P = 0.03) and vitamin K status improved as demonstrated by a decreased percentage of undercarboxylated osteocalcin of -6.0% ± 1.6% by 12 months (adjusted R2 = 0.15, P < 0.001). These changes occurred in both the LXS and placebo comparison groups. No changes in serum 25D or α-tocopherol were detected. Both nutrition interventions increased caloric intake a mean of 83 ± 666 kcal/day by 12 months. CONCLUSIONS Vitamins A and K status improved, whereas vitamins D and E status was unchanged during 12 months of LXS and isocaloric placebo comparison supplement in children with CF and PI.
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Affiliation(s)
- Chiara Bertolaso
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA
| | - Veronique Groleau
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA
| | - Joan I. Schall
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA
| | - Asim Maqbool
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Maria Mascarenhas
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Norma Latham
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA
| | - Kelly A. Dougherty
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Virginia A. Stallings
- Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Bone turnover markers, osteoprotegerin and RANKL cytokines in children with cystic fibrosis. Adv Med Sci 2013; 58:338-43. [PMID: 24277958 DOI: 10.2478/ams-2013-0011] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
PURPOSE Some scientific studies show decreased bone mineral density and increased fracture frequency in adult patients with cystic fibrosis (CF). The mechanism for early bone loss in CF patients are multifactorial: chronic pulmonary inflammation, malnutrition, reduced physical activity, delayed pubertal maturation. The aim of this study was to assess bone metabolism markers with special attention paid to osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) balance in CF children. MATERIAL AND METHODS The study included 35 children with diagnosed CF and 35 healthy controls aged 5-9 years (median 7.0 years). Serum levels of fat soluble vitamins were measured by chemiluminescence (vitamin D) and HPLC (vitamins A, E) methods. Concentrations of bone metabolism markers were determined by immunoenzymatic assay. RESULTS Mean levels of fat soluble vitamins (A, D, E) were lower in patients with CF compared to controls. In CF children we observed a significant (p<0.01) decrease in concentration of bone formation marker (osteocalcin) and similar bone resorption markers (CTX, TRACP5b) in comparison with healthy children. The serum level of OPG was significantly lower (p<0.05) and RANKL nearly 2-fold higher in patients with CF than in the healthy ones. The ratio of OPG to RANKL was about 2-fold lower in children with CF compared to healthy peers (p<0.01). CONCLUSION In CF children, an imbalance between bone formation and resorption processes occurs. An increase serum RANKL concentration coexisting with lower levels of OPG may be associated with intensification of bone resorption.
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Abstract
Despite the inclusion of extra vitamin D in their regimen of fat-soluble vitamin supplementation, cystic fibrosis patients remain chronically depleted of vitamin D. The persistence of suboptimal vitamin D status is often blamed on the maldigestion and malabsorption of fat. However, the mitigated success of recent clinical trials with high-dose vitamin D supplementation suggests that vitamin D bioavailability might be impaired in these patients. Given the growing understanding of the importance of this vitamin in the regulation of multiple biological functions beyond skeletal health, the present review analyzes the current literature by addressing each step of vitamin D metabolism and action in the context of this life-limiting pathology. In addition, it highlights the importance of vitamin D in relation to organs and or conditions affected by cystic fibrosis.
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Affiliation(s)
- Geneviève Mailhot
- Research Centre, CHU Sainte-Justine, Department of Nutrition, Université de Montréal, Montréal, Canada.
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17
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Vitamin D receptor agonists inhibit pro-inflammatory cytokine production from the respiratory epithelium in cystic fibrosis. J Cyst Fibros 2011; 10:428-34. [PMID: 21784717 DOI: 10.1016/j.jcf.2011.06.013] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2011] [Revised: 06/11/2011] [Accepted: 06/28/2011] [Indexed: 01/28/2023]
Abstract
BACKGROUND 1,25-Dihydroxycholecalciferol (1,25(OH)(2)D(3)) has been shown to mitigate epithelial inflammatory responses after antigen exposure. Patients with cystic fibrosis (CF) are at particular risk for vitamin D deficiency. This may contribute to the exaggerated inflammatory response to pulmonary infection in CF. METHODS CF respiratory epithelial cell lines were exposed to Pseudomonas aeruginosa lipopolysaccharide (LPS) and Pseudomonas conditioned medium (PCM) in the presence or absence of 1,25(OH)(2)D(3) or a range of vitamin D receptor (VDR) agonists. Levels of IL-6 and IL-8 were measured in cell supernatants, and cellular total and phosphorylated IκBα were determined. Levels of human cathelicidin antimicrobial peptide (hCAP18) mRNA and protein were measured in cells after treatment with 1,25(OH)(2)D(3). RESULTS Pretreatment with 1,25(OH)(2)D(3) was associated with significant reductions in IL-6 and IL-8 protein secretion after antigen exposure, a finding reproduced with a range of low calcaemic VDR agonists. 1,25(OH)(2)D(3) treatment led to a decrease in IκBα phosphorylation and increased total cellular IκBα. Treatment with 1,25(OH)(2)D(3) was associated with an increase in hCAP18/LL-37 mRNA and protein levels. CONCLUSIONS Both 1,25(OH)(2)D(3) and other VDR agonists significantly reduce the pro-inflammatory response to antigen challenge in CF airway epithelial cells. VDR agonists have significant therapeutic potential in CF.
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18
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Sunlight is an important determinant of vitamin D serum concentrations in cystic fibrosis. Eur J Clin Nutr 2011; 65:574-9. [DOI: 10.1038/ejcn.2010.280] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Green DM, Leonard AR, Paranjape SM, Rosenstein BJ, Zeitlin PL, Mogayzel PJ. Transient effectiveness of vitamin D2 therapy in pediatric cystic fibrosis patients. J Cyst Fibros 2010; 9:143-9. [DOI: 10.1016/j.jcf.2010.01.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2009] [Revised: 01/04/2010] [Accepted: 01/13/2010] [Indexed: 10/19/2022]
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Hall WB, Sparks AA, Aris RM. Vitamin d deficiency in cystic fibrosis. Int J Endocrinol 2010; 2010:218691. [PMID: 20148079 PMCID: PMC2817861 DOI: 10.1155/2010/218691] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2009] [Revised: 09/01/2009] [Accepted: 10/23/2009] [Indexed: 11/21/2022] Open
Abstract
Cystic Fibrosis is the most common inherited genetic respiratory disorder in the Western World. Hypovitaminosis D is almost universal in CF patients, likely due to a combination of inadequate absorption, impaired metabolism, and lack of sun exposure. Inadequate levels are associated with the high prevalence of bone disease or osteoporosis in CF patients, which is associated with increased morbidity including fractures, kyphosis, and worsening pulmonary status. Treatment goals include regular monitoring 25 hydroxyvitamin D (25OHD) levels with aggressive treatment for those with levels <75 nmol/L (<30 ng/mL). More research is needed to determine optimal supplementation goals and strategies.
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Affiliation(s)
- William B. Hall
- Division of Pulmonary and Critical Care Medicine and the
School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Amy A. Sparks
- Division of Pulmonary and Critical Care Medicine and the
School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Robert M. Aris
- Division of Pulmonary and Critical Care Medicine and the
School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- *Robert M. Aris:
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Very high-dose ergocalciferol is effective for correcting vitamin D deficiency in children and young adults with cystic fibrosis. J Cyst Fibros 2009; 8:270-2. [PMID: 19447079 DOI: 10.1016/j.jcf.2009.04.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2009] [Revised: 03/17/2009] [Accepted: 04/03/2009] [Indexed: 11/21/2022]
Abstract
Approximately 10-80% of patients with Cystic Fibrosis (CF) have vitamin D deficiency. Obtaining therapeutic vitamin D levels has been a challenge for CF care providers using current recommended high-dose oral ergocalciferol (400,000 IU over 2 months). The objective of this study was to evaluate the safety and efficacy of a 2-week, very high dose ergocalciferol (700,000 IU over 14 days) repletion strategy in children and young adults with CF. As part of a quality improvement initiative, a prospective cohort study was performed from January through May 2007. Phase I included identifying individuals with CF who were subtherapeutic in 25-OH D. In phase II, 50,000 IU of ergocalciferol was prescribed for a 14 day term and administered daily. During phase III, a post treatment 25-OH D level was obtained to determine improvement. Baseline demographics and clinical characteristics were obtained at study entry. Stratification of the post 25-OHD levels was defined. Eighteen individuals with CF participated in the study. The mean age was 17+/-5 years (range 6-25 years). One hundred percent were pancreatic insufficient and required pancreatic enzyme replacement. All 18 had 25-OHD levels less than 30 ng/mL pre-treatment. Seventeen of the 18 (94%) participants became therapeutic in the 2-week interval. No patients had values considered high abnormal (100-150 ng/mL) or toxic (>150 ng/mL). Mean change was noted at an increase of 37.3+/-22 ng/mL in the 2-week period (p<0.001). Pre and peripubertal individuals had a significantly greater increase in 25-OH D levels. The results of this study demonstrate that very high dosing of vitamin D using oral ergocalciferol over a 14 day period is an effective strategy in achieving therapeutic levels of 25-OH vitamin D in children and young adults with CF. We believe this regimen deserves further study.
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DiVasta AD, van der Veen KK, Gordon CM. Vitamin D Deficiency in Children and Its Health Consequences. Clin Rev Bone Miner Metab 2009. [DOI: 10.1007/s12018-009-9036-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Neville LA, Ranganathan SC. Vitamin D in infants with cystic fibrosis diagnosed by newborn screening. J Paediatr Child Health 2009; 45:36-41. [PMID: 19208064 DOI: 10.1111/j.1440-1754.2008.01432.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
AIMS Screening enables early nutritional deficiencies to be detected in those with cystic fibrosis (CF). Although vitamin deficiency is considered unlikely in older subjects with normal vitamin E levels, few studies have determined vitamin D status at diagnosis and its relationship to other fat-soluble vitamins. METHODS We reviewed vitamin levels in infants diagnosed with CF by newborn screening over a 5-year period in Melbourne, Australia. Vitamin D levels were determined using the IDS gamma-B 25-OH Vitamin D radio-immunoassay (Immunodiagnostic Systems Limited, Boldon, UK). Vitamins A and E were evaluated by high-performance liquid chromatography. We assessed the association between vitamin D level and sex, month of birth, pancreatic status, and vitamin A and E levels. RESULTS Fifty-eight infants were diagnosed at a median age of 1 month (range: 0-3 months). Initial vitamin D levels were assessed between 0.2 and 3.5 months in 30 (vitamin D) and 45 (vitamins A and E) infants. The number of infants deficient with vitamins D, E and A were 11 (37%), 7 (16%) and 27 (60%), respectively. Vitamin D levels were unrelated to sex, vitamin A or E levels, month of birth or pancreatic status, whereas vitamin A and E levels were significantly lower in those who were pancreatic insufficient. With supplementation, vitamin D increased over time. CONCLUSIONS Vitamin D deficiency is common in infants newly diagnosed with CF by newborn screening and is unrelated to pancreatic status or predicted low vitamin E levels. Vitamin D deficiency is less common over time following treatment.
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Affiliation(s)
- Liza A Neville
- Department of Respiratory Medicine, Royal Children's Hospital, Melbourne Vic., Australia
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Grey V, Atkinson S, Drury D, Casey L, Ferland G, Gundberg C, Lands LC. Prevalence of low bone mass and deficiencies of vitamins D and K in pediatric patients with cystic fibrosis from 3 Canadian centers. Pediatrics 2008; 122:1014-20. [PMID: 18977981 DOI: 10.1542/peds.2007-2336] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE In this cross-sectional observational study, we assessed both vitamins D and K status and bone health in pancreatic insufficient pediatric patients with cystic fibrosis from 3 Canadian cystic fibrosis centers. METHODS Eighty-one patients who had cystic fibrosis and were clinically stable for at least 3 months were enrolled. At the time of the clinic visit, anthropometric variables, lung function, pubertal status, intake of calcium and vitamins D and K, and physical activity were assessed. Blood was taken for analysis of biochemical biomarkers of bone turnover and status of vitamins D and K, and a urine sample was obtained for calcium, creatinine, sodium, and deoxypyridoline analyses. Whole-body bone mineral content and lumbar spine (L1-L4) bone mineral density were measured. RESULTS The children were relatively well nourished and had moderate to mild lung disease. Low bone mineral mass defined as a z score between -1.0 and -2.0, for gender and age was detected in 38% of the children for whole body and in 28% for lumbar spine. z score less than -2.0 was observed in 7 children for both bone measures. Suboptimal vitamin D status occurred in 95% of patients; suboptimal vitamin K status occurred in 82% of patients. Measures of plasma osteocalcin and carboxy-terminal propeptide type 1 procollagen and urinary deoxypyridoline compared with reference values for age, gender, and pubertal status reflected a state of suppressed bone formation and elevated bone resorption in a large proportion of the patients. CONCLUSIONS Bone mass of the whole body and spine was lower than expected for chronological age in approximately one third of pediatric patients with cystic fibrosis irrespective of gender or age. This may be explained by the observation of low bone turnover for developmental stage as indicated by bone biomarkers. Suboptimal status of vitamins D and K may be key causative factors of the low bone status for age.
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Current treatment recommendations for correcting vitamin D deficiency in pediatric patients with cystic fibrosis are inadequate. J Pediatr 2008; 153:554-9. [PMID: 18589445 DOI: 10.1016/j.jpeds.2008.04.058] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2007] [Revised: 03/20/2008] [Accepted: 04/24/2008] [Indexed: 11/20/2022]
Abstract
OBJECTIVES To determine the prevalence of vitamin D deficiency (25-hydroxy vitamin D [25-OHD] levels in plasma <30 ng/mL) in pediatric patients with cystic fibrosis (CF), elucidate contributing factors for vitamin D deficiency, and determine the efficacy of ergocalciferol repletion strategies. STUDY DESIGN Retrospective chart review of 262 pediatric patients from January 2003 to December 2006 with linear and logistic regression analyses. RESULTS Vitamin D deficiency prevalence declined in the years studied from 86.5% to 46.2%. Patients >12 years old were more likely to have deficiency than patients <5 years old (odds ratio [OR], 3.44; 95% CI, 1.73-6.84). Levels obtained in spring and summer were less likely to be deficient compared with those obatained in fall (OR, 0.24; 95% CI, 0.10-0.61; and OR, 0.25; 95% CI, 0.11-0.61; respectively). Success of treatment with 50,000 IU of ergocalciferol once, twice, or 3 times weekly was 33%, 26%, and 43%, respectively. Ergocalciferol, when compared with no treatment, did not significantly increase the proportion of patients with follow-up levels > or =30 ng/mL (chi(2)P value = .80, .34, and .22, respectively). CONCLUSIONS The prevalence of vitamin D deficiency is high, but declined with time. Age, forced expiratory volume in 1 second, and season were associated with 25-OHD levels. Despite 33% of patients responding to 50 000 IU of ergocalciferol once a week, this recommendation does not adequately treat most patients with CF who have vitamin D deficiency.
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Rovner AJ, Stallings VA, Schall JI, Leonard MB, Zemel BS. Vitamin D insufficiency in children, adolescents, and young adults with cystic fibrosis despite routine oral supplementation. Am J Clin Nutr 2007; 86:1694-9. [PMID: 18065588 DOI: 10.1093/ajcn/86.5.1694] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Cystic fibrosis (CF) with pancreatic insufficiency is associated with poor absorption of fat and fat-soluble vitamins, including vitamin D. Pancreatic enzyme supplementation does not completely correct fat malabsorption in CF patients. OBJECTIVE The objective of the study was to compare the vitamin D status of children, adolescents, and young adults with CF who were treated with routine vitamin D and pancreatic enzyme supplements with the vitamin D status of a healthy reference group from a similar geographic area. DESIGN Growth, dietary intake, and serum concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and parathyroid hormone (PTH) were measured in 101 white subjects with CF and a reference group of 177 white subjects. RESULTS The median daily vitamin D supplementation in the CF group was 800 IU. The mean +/- SD serum concentrations of 25(OH)D were 20.7 +/- 6.5 ng/mL in the CF group and 26.2 +/- 8.6 ng/mL in the reference group (P < 0.001). Vitamin D deficiency and insufficiency were defined as 25(OH)D concentrations < 11 ng/mL and < 30 ng/mL, respectively. Seven percent of the CF group and 2% of the healthy reference group were vitamin D deficient (P < 0.03). Ninety percent of the CF group and 74% of the healthy reference group were vitamin D insufficient (P < 0.01). Twenty-five percent of the CF group and 9% of the healthy reference group had elevated PTH (P < 0.006). The odds of vitamin D insufficiency in the CF group, compared with the healthy reference group, were 1.2 (95% CI: 1.1, 1.3) after adjustment for season and age. CONCLUSION Despite daily vitamin D supplementation, serum 25(OH)D concentrations remain low in children, adolescents, and young adults with CF.
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Affiliation(s)
- Alisha J Rovner
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
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