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Papadimitriou DT, Dermitzaki E, Christopoulos P, Papagianni M, Kleanthous K, Marakaki C, Papadimitriou A, Mastorakos G. Secondary Prevention of Diabetes Type 1 with Oral Calcitriol and Analogs, the PRECAL Study. CHILDREN (BASEL, SWITZERLAND) 2023; 10:862. [PMID: 37238410 PMCID: PMC10217040 DOI: 10.3390/children10050862] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 05/04/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023]
Abstract
Screening for Type 1 Diabetes (T1D, incidence 1:300) with T1D autoantibodies (T1Ab) at ages 2 and 6, while sensitive, lacks a preventive strategy. Cholecalciferol 2000 IU daily since birth reduced T1D by 80% at 1 year. T1D-associated T1Ab negativized within 0.6 years with oral calcitriol in 12 children. To further investigate secondary prevention of T1D with calcitriol and its less calcemic analog, paricalcitol, we initiated a prospective interventional non-randomized clinical trial, the PRECAL study (ISRCTN17354692). In total, 50 high-risk children were included: 44 were positive for T1Ab, and 6 had predisposing for T1D HLA genotypes. Nine T1Ab+ patients had variable impaired glucose tolerance (IGT), four had pre-T1D (3 T1Ab+, 1 HLA+), nine had T1Ab+ new-onset T1D not requiring insulin at diagnosis. T1Ab, thyroid/anti-transglutaminase Abs, glucose/calcium metabolism were determined prior and q3-6 months on calcitriol, 0.05 mcg/Kg/day, or paricalcitol 1-4 mcg × 1-3 times/day p.o. while on cholecalciferol repletion. Available data on 42 (7 dropouts, 1 follow-up < 3 months) patients included: all 26 without pre-T1D/T1D followed for 3.06 (0.5-10) years negativized T1Ab (15 +IAA, 3 IA2, 4 ICA, 2 +GAD, 1 +IAA/+GAD, 1 +ICA/+GAD) within 0.57 (0.32-1.3) years or did not develop to T1D (5 +HLA, follow-up 3 (1-4) years). From four pre-T1D cases, one negativized T1Ab (follow-up 1 year), one +HLA did not progress to T1D (follow-up 3.3 years) and two +T1Ab patients developed T1D in 6 months/3 years. Three out of nine T1D cases progressed immediately to overt disease, six underwent complete remission for 1 year (1 month-2 years). Five +T1Ab patients relapsed and negativized again after resuming therapy. Four (aged <3 years) negativized anti-TPO/TG, and two anti-transglutaminase-IgA. Eight presented mild hypercalciuria/hypercalcemia, resolving with dose titration/discontinuation. Secondary prevention of T1D with calcitriol and paricalcitol seems possible and reasonably safe, if started soon enough after seroconversion.
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Affiliation(s)
- Dimitrios T. Papadimitriou
- Second Department of Obstetrics and Gynecology, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Department of Pediatric-Adolescent Endocrinology and Diabetes, Athens Medical Center, 15125 Marousi, Greece
| | - Eleni Dermitzaki
- Department of Pediatric-Adolescent Endocrinology and Diabetes, Athens Medical Center, 15125 Marousi, Greece
| | - Panagiotis Christopoulos
- Second Department of Obstetrics and Gynecology, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Maria Papagianni
- Department of Nutrition and Dietetics, University of Thessaly, 42132 Trikala, Greece
- Unit of Endocrinology, Diabetes and Metabolism, Third Department of Pediatrics, Aristotle University of Thessaloniki, Hippokrateion Hospital of Thessaloniki, 54642 Thessaloniki, Greece
| | - Kleanthis Kleanthous
- Department of Pediatric-Adolescent Endocrinology and Diabetes, Athens Medical Center, 15125 Marousi, Greece
| | - Chrysanthi Marakaki
- Department of Pediatric-Adolescent Endocrinology and Diabetes, Athens Medical Center, 15125 Marousi, Greece
| | - Anastasios Papadimitriou
- Pediatric Endocrinology Unit, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Haidari, Greece
| | - George Mastorakos
- Second Department of Obstetrics and Gynecology, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
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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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Liu Y, Clare S, D'Erasmo G, Heilbronner A, Dash A, Krez A, Zaworski C, Haseltine K, Serota A, Miller A, Veiga K, Sandoval M, T Lu T, McMahon DJ, Nieves JW, Stein EM. Vitamin D and SARS-CoV-2 Infection: SERVE Study (SARS-CoV-2 Exposure and the Role of Vitamin D among Hospital Employees). J Nutr 2023; 153:1420-1426. [PMID: 36871833 PMCID: PMC9985522 DOI: 10.1016/j.tjnut.2023.03.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 02/27/2023] [Accepted: 03/01/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Recognition of the role of vitamin D in immune function has led to interest in its relationship with SARS-CoV-2 infection. Although clinical studies to date have had conflicting results, many individuals currently take high doses of vitamin D to prevent infection. The goal of this study was to investigate the relationship between serum 25-hydroxyvitamin D (25OHD) and vitamin D supplement use with incident SARS-CoV-2 infection. METHODS In this prospective cohort study, 250 health care workers were enrolled at a single institution and observed for 15 mo. Participants completed questionnaires every 3 mo regarding new SARS-CoV-2 infection, vaccination, and supplement use. Serum was drawn at baseline, 6, and 12 mo for 25OHD and SARS-CoV-2 nucleocapsid antibodies. RESULTS The mean age of the participants was 40 y, BMI 26 kg/m2, 71% were Caucasian, and 78% female. Over 15 mo, 56 participants (22%) developed incident SARS-CoV-2 infections. At baseline, ∼50% reported using vitamin D supplements (mean daily dose 2250 units). Mean serum 25OHD was 38 ng/mL. Baseline 25OHD did not predict incident SARS-CoV-2 infection (OR: 0.98; 95% CI: 0.80, 1.20). Neither the use of vitamin D supplements (OR: 1.18; 95% CI: 0.65, 2.14) or supplement dose was associated with incident infection (OR: 1.01 per 100-units increase; 95% CI: 0.99, 1.02). CONCLUSION In this prospective study of health care workers, neither serum 25OHD nor the use of vitamin D supplements was associated with the incident SARS-CoV-2 infection. Our findings argue against the common practice of consuming high-dose vitamin D supplements for the presumed prevention of COVID-19.
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Affiliation(s)
- Yi Liu
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Shannon Clare
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Gia D'Erasmo
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Alison Heilbronner
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Alexander Dash
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Alexandra Krez
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Caroline Zaworski
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Katherine Haseltine
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Alana Serota
- Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Andy Miller
- Division of Infectious Diseases, Hospital for Special Surgery, New York, NY, United States
| | - Keila Veiga
- Research Institute, Hospital for Special Surgery, New York, NY, United States
| | - Marvin Sandoval
- Research Institute, Hospital for Special Surgery, New York, NY, United States
| | - Theresa T Lu
- Research Institute, Hospital for Special Surgery, New York, NY, United States
| | - Donald J McMahon
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Jeri W Nieves
- Metabolic Bone Service, Hospital for Special Surgery, New York, United States
| | - Emily Margaret Stein
- Division of Endocrinology, Hospital for Special Surgery, New York, NY, United States; Metabolic Bone Service, Hospital for Special Surgery, New York, United States; Research Institute, Hospital for Special Surgery, New York, NY, United States.
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Ali HA, Deraz TE, Mohamed DA, Mahmoud MZ. Impact of vitamin D status on CF and non-CF bronchiectasis outcomes. EGYPTIAN PEDIATRIC ASSOCIATION GAZETTE 2022. [DOI: 10.1186/s43054-021-00095-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Vitamin D deficiency occurs frequently in cystic fibrosis (CF) and non-CF bronchiectasis patients. Yet, few studies have assessed the impact of vitamin D status on the clinical outcomes in pediatric bronchiectasis. This study is designed to assess vitamin D level and determine its effect on exacerbations, bacterial colonization, and lung function in pediatric patients with CF and non-CF bronchiectasis.
Results
This cross-sectional case-control study assessing vitamin D level was performed in a total of sixty cases under the age of 18 years—forty cases with CF and non-CF bronchiectasis and twenty age- and sex-matched healthy controls. Associations between serum vitamin D and clinical and laboratory parameters were assessed in the patient groups. Vitamin D deficiency was more prevalent among CF and non-CF bronchiectasis patients (75%, 45%) compared to controls (10%) (P < 0.001). In addition, vitamin D deficiency was associated with more frequent and severe pulmonary exacerbations (66.7%, 46.7%) (P=0.033, < 0.001), chronic Pseudomonas infection (80%) (P=0.060) among CF patients, and with lower FEV1 (66%) (P= 0.071) among non-CF bronchiectasis. Moreover, a cutoff value of vitamin D level equal or less than 22.5 ng/ml was accurate in differentiating moderate from mild pulmonary exacerbations in both patients’ groups (AUC=0.809) (p=0.004).
Conclusions
Vitamin D deficiency is not uncommon in both CF and non-CF bronchiectasis. In this population, vitamin D deficiency is associated with more frequent pulmonary exacerbations, chronic Pseudomonas infection, and worse lung function.
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Bojanowski CM, Lu S, Kolls JK. Mucosal Immunity in Cystic Fibrosis. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2021; 207:2901-2912. [PMID: 35802761 PMCID: PMC9270582 DOI: 10.4049/jimmunol.2100424] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 10/21/2021] [Indexed: 05/27/2023]
Abstract
The highly complex and variable genotype-phenotype relationships observed in cystic fibrosis (CF) have been an area of growing interest since the discovery of the CF transmembrane conductance regulator (CFTR) gene >30 y ago. The consistently observed excessive, yet ineffective, activation of both the innate and adaptive host immune systems and the establishment of chronic infections within the lung, leading to destruction and functional decline, remain the primary causes of morbidity and mortality in CF. The fact that both inflammation and pathogenic bacteria persist despite the introduction of modulator therapies targeting the defective protein, CFTR, highlights that we still have much to discover regarding mucosal immunity determinants in CF. Gene modifier studies have overwhelmingly implicated immune genes in the pulmonary phenotype of the disease. In this context, we aim to review recent advances in our understanding of the innate and adaptive immune systems in CF lung disease.
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Affiliation(s)
- Christine M Bojanowski
- Section of Pulmonary Diseases, Critical Care, and Environmental Medicine, Department of Medicine, Tulane University School of Medicine, New Orleans, LA;
| | - Shiping Lu
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA; and
| | - Jay K Kolls
- Center for Translational Research in Infection and Inflammation, Department of Medicine, Tulane University School of Medicine, New Orleans, LA
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Upadhaya SD, Chung TK, Jung YJ, Kim IH. Dietary 25(OH)D3 supplementation to gestating and lactating sows and their progeny affects growth performance, carcass characteristics, blood profiles and myogenic regulatory factor- related gene expression in wean-finish pigs. Anim Biosci 2021; 35:461-474. [PMID: 34727644 PMCID: PMC8902224 DOI: 10.5713/ab.21.0304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/21/2021] [Indexed: 11/27/2022] Open
Abstract
Objective This experiment investigated the effects of supplementing vitamin D3-fortified sow and progeny diets with 25(OH)D3 on growth performance, carcass characteristics, immunity, and pork meat quality. Methods The present study involved the assessment of supplementing the diet of sows and their progeny with or without 25 (OH)D3 in a 2×2 factorial arrangement on the performance and production characteristics of wean-finish pigs. Forty-eight multiparous sows were assigned to a basal diet containing 2000 IU/kg vitamin D3 and supplemented without (CON) or with (TRT) 50 μg/kg 25 (OH)D3. At weaning, a total of 80 pigs each from CON and TRT sows were allocated to weaning and growing-finishing basal diets fortified with 2,500 and 1,750 IU/kg vitamin D3 respectively and supplemented without or with 50 μg/kg 25(OH)D3. Results Sows fed 25(OH)D3-supplemented diets improved pre-weaning growth rate of nursing piglets. A significant sow and pig weaning diet effect was observed for growth rate and feed efficiency (p<0.05) during days 1 to 42 post-weaning. Pigs consuming 25(OH)D3-supplemented diets gained weight faster (p = 0.016), ate more (p = 0.044) and tended to convert feed to gain more efficiently (p = 0.088) than those fed CON diet between days 98 and 140 post-weaning. Supplemental 25(OH)D3 improved water holding capacity and reduced drip loss of pork meat, increased serum 25(OH)D3 level, produced higher interleukin-1 and lower interleukin-6 concentrations in blood circulation, downregulated myostatin (MSTN) and upregulated myogenic differentiation (MYOD) and myogenic factor 5 (MYF5) gene expressions (p<0.05). Conclusion Supplementing vitamin D3-fortified sow and wean-finish pig diets with 50 μg/kg 25(OH)D3 significantly improved production performance suggesting their current dietary vitamin D3 levels are insufficient. In fulfilling the total need for vitamin D, it is strongly recommended to add 50 μg/kg 25(OH)D3 “on top” to practical vitamin D3-fortified sow and wean-finish pig diets deployed under commercial conditions.
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Affiliation(s)
- Santi Devi Upadhaya
- Department of Animal Resource and Science, Dankook University, Cheonan, 31116, Korea
| | - Thau Kiong Chung
- DSM Nutritional Products Asia Pacific, Mapletree Business City, Singapore 117440, MapleTree Business City, Singapore
| | - Yeon Jae Jung
- Department of Animal Resource and Science, Dankook University, Cheonan, 31116, Korea
| | - In Ho Kim
- Department of Animal Resource and Science, Dankook University, Cheonan, 31116, Korea
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Loukou I, Moustaki M, Sardeli O, Plyta M, Douros K. Association of vitamin D status with lung function measurements in children and adolescents with cystic fibrosis. Pediatr Pulmonol 2020; 55:1375-1380. [PMID: 31338968 DOI: 10.1002/ppul.24460] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Accepted: 07/09/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Vitamin D status is considered a potential determinant of lung function in cystic fibrosis (CF). The aim of this retrospective longitudinal study was to investigate the decline of spirometric values in association with vitamin D status. METHODS The data regarding 25-hydroxy vitamin D (25OHD) serum levels, spirometric measurements (FEV1, FVC, FEF25-75%), and factors known to be associated with the decline of lung function in CF were retrospectively collected over a 5-year period. The spirometric indices were recorded as the best and the average value of each year, as well as the value, recorded concurrently or closely with 25OHD level measurement. RESULTS A significantly positive relationship was observed between 25OHD serum levels and the best annual value of FEV1 (P = .034), and the values of FEV1 (P = .010) and FVC (P = .018) measured concurrently or closely with serum 25OHD levels. The evolution of the best annual value of FEV1 was worse in patients with a mean 5-year value of 25OHD levels less than 20 ng/mL compared with patients with a mean 5-year value of ≥30 ng/mL (P < .001), or ≥20 to <30 (P < .001). There was no significant difference between patients with mean 5-year 25OHD levels ≥30 ng/mL and ≥20 to <30 ng/mL (P = .76). CONCLUSIONS Vitamin D status is associated with lung function in patients with CF. Levels of 25OHD above 20 ng/mL were associated with higher best annual FEV1.
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Affiliation(s)
- Ioanna Loukou
- Cystic Fibrosis Department, "Agia Sofia" Children's Hospital, Athens, Greece
| | - Maria Moustaki
- Cystic Fibrosis Department, "Agia Sofia" Children's Hospital, Athens, Greece
| | - Olympia Sardeli
- Pediatric Allergy and Respiratory Unit, 3rd Department of Pediatrics, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athen, Athens, Greece
| | - Marina Plyta
- Cystic Fibrosis Department, "Agia Sofia" Children's Hospital, Athens, Greece
| | - Konstantinos Douros
- Pediatric Allergy and Respiratory Unit, 3rd Department of Pediatrics, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athen, Athens, Greece
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Miclea A, Bagnoud M, Chan A, Hoepner R. A Brief Review of the Effects of Vitamin D on Multiple Sclerosis. Front Immunol 2020; 11:781. [PMID: 32435244 PMCID: PMC7218089 DOI: 10.3389/fimmu.2020.00781] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/06/2020] [Indexed: 12/15/2022] Open
Abstract
Multiple sclerosis (MS) is characterized as an autoimmune disease affecting the central nervous system. It is one of the most common neurological disorders in young adults. Over the past decades, increasing evidence suggested that hypovitaminosis D is a contributing factor to the risk of developing MS. From different risk factors contributing to the development of MS, vitamin D status is of particular interest since it is not only a modifiable risk factor but is also associated with MS disease activity. MS patients with lower serum vitamin D concentrations were shown to have higher disease activity. However, this finding does not demonstrate causality. In this regard, prospective vitamin D supplementation studies missed statistical significance in its primary endpoints but showed promising results in secondary outcome measures or post hoc analyses. An explanation for missed primary endpoints may be underpowered trials. Besides vitamin D supplementation as a potential add-on to long-term immunotherapeutic treatment, a recent laboratory study of our group pointed toward a beneficial effect of vitamin D to improve the efficacy of glucocorticoids in relapse therapy. In the following article, we will briefly review the effects of vitamin D on MS by outlining its effects on the immune and nervous system and by reviewing the association between vitamin D and MS risk as well as MS disease activity. We will also review the effects of vitamin D supplementation on MS risk and MS disease activity.
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Affiliation(s)
- Andrei Miclea
- Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland
| | - Maud Bagnoud
- Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland
| | - Andrew Chan
- Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland
| | - Robert Hoepner
- Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland
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9
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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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Trend S, Jones AP, Cha L, Byrne SN, Geldenhuys S, Fabis-Pedrini MJ, Carroll WM, Cole JM, Booth DR, Lucas RM, Kermode AG, French MA, Hart PH. Higher Serum Immunoglobulin G3 Levels May Predict the Development of Multiple Sclerosis in Individuals With Clinically Isolated Syndrome. Front Immunol 2018; 9:1590. [PMID: 30057580 PMCID: PMC6053531 DOI: 10.3389/fimmu.2018.01590] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 06/27/2018] [Indexed: 11/13/2022] Open
Abstract
Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1–4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein–Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of “upstream” to “downstream” IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS.
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Affiliation(s)
- Stephanie Trend
- Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
| | - Anderson P Jones
- Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
| | - Lilian Cha
- Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
| | - Scott N Byrne
- Sydney Medical School, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia
| | - Sian Geldenhuys
- Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
| | - Marzena J Fabis-Pedrini
- Centre for Neuromuscular and Neurological Disorders, Perron Institute for Neurological and Translational Science, Sir Charles Gairdner Hospital, University of Western Australia, Perth, WA, Australia
| | - William M Carroll
- Centre for Neuromuscular and Neurological Disorders, Perron Institute for Neurological and Translational Science, Sir Charles Gairdner Hospital, University of Western Australia, Perth, WA, Australia
| | - Judith M Cole
- St John of God Dermatology Clinic, St John of God Hospital, Perth, WA, Australia
| | - David R Booth
- Sydney Medical School, Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia
| | - Robyn M Lucas
- National Centre for Epidemiology & Population Health, Research School of Population Health, Australian National University, Canberra, ACT, Australia.,Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, WA, Australia
| | - Allan G Kermode
- Centre for Neuromuscular and Neurological Disorders, Perron Institute for Neurological and Translational Science, Sir Charles Gairdner Hospital, University of Western Australia, Perth, WA, Australia.,Institute for Immunology and Infectious Disease, Murdoch University, Perth, WA, Australia
| | - Martyn A French
- UWA Medical School and School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia
| | - Prue H Hart
- Telethon Kids Institute, University of Western Australia, Perth, WA, Australia
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11
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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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12
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Thursfield RM, Naderi K, Leaver N, Rosenthal M, Alton EWFW, Bush A, Davies JC. Children with cystic fibrosis demonstrate no respiratory immunological, infective or physiological, consequences of vitamin D deficiency. J Cyst Fibros 2018; 17:657-665. [PMID: 29631774 DOI: 10.1016/j.jcf.2018.02.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 02/25/2018] [Accepted: 02/26/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND Vitamin D has health benefits in many respiratory diseases but the evidence in CF is unclear. Induction of the antimicrobial peptides cathelicidin (LL37) and human-beta-defensin-2 (HBD-2) may be the mechanism of any benefit. We hypothesised that antimicrobial peptide levels would be decreased, and airway infection and inflammation greater, in CF children with vitamin D deficiency. The objective of the study was to explore relationships between vitamin D, LL37 and HBD-2, and airway infection, inflammation and physiology in children with CF. METHODS Bronchoalveolar lavage (BALF) and blood were obtained from children undergoing fibreoptic bronchoscopy. Serum vitamin D, BALF HBD-2 and LL37, cultured bacteria and inflammatory markers were measured. Clinical parameters were recorded. RESULTS 113 patients with CF, 23 with non-CF chronic suppurative lung disease (CSLD) and 6 healthy controls were included. We found no relationship between serum vitamin D and BALF HBD-2 or LL-37. There were no differences in infective or inflammatory markers between vitamin D sufficient and deficient groups. Vitamin D deficient patients (<50 nmol/L) did not have a worse FEV1 (CF: 66 (58-71)% vs. 71.5 (61-76)%, ns; non-CF CSLD: 69 (36-88)% vs. 70 (62-95)%, ns). CONCLUSIONS In the first bronchoscopic study exploring this question, we demonstrate that vitamin D deficiency is not associated with immunological, infective or clinical markers of disease severity in patients with CF or CSLD.
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Affiliation(s)
- Rebecca M Thursfield
- National Heart and Lung Institute, Imperial College, London, United kingdom; Department of Paediatric Respiratory Medicine, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom.
| | - Khayam Naderi
- National Heart and Lung Institute, Imperial College, London, United kingdom
| | - Neil Leaver
- Department of Immunosuppression Monitoring, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom
| | - Mark Rosenthal
- Department of Paediatric Respiratory Medicine, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom
| | - Eric W F W Alton
- National Heart and Lung Institute, Imperial College, London, United kingdom
| | - Andrew Bush
- National Heart and Lung Institute, Imperial College, London, United kingdom; Department of Paediatric Respiratory Medicine, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom
| | - Jane C Davies
- National Heart and Lung Institute, Imperial College, London, United kingdom; Department of Paediatric Respiratory Medicine, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom
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13
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Dąbrowska-Leonik N, Bernatowska E, Pac M, Filipiuk W, Mulawka J, Pietrucha B, Heropolitańska-Pliszka E, Bernat-Sitarz K, Wolska-Kuśnierz B, Mikołuć B. Vitamin D deficiency in children with recurrent respiratory infections, with or without immunoglobulin deficiency. Adv Med Sci 2018; 63:173-178. [PMID: 29128760 DOI: 10.1016/j.advms.2017.08.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 07/22/2017] [Accepted: 08/22/2017] [Indexed: 01/04/2023]
Abstract
PURPOSE The objective of this study was to evaluate thevitamin D concentration in patients with recurrent respiratory infections with or without immunoglobulin G, A or M (IgG, IgA, IgM) deficiency, and to find a correlation between the vitamin D concentration and the response to hepatitis B vaccination. MATERIALS AND METHOD The study involved 730 patients with recurrent respiratory infections. The concentration of 25-hydroxyvitamin D (25(OH)D), immunoglobulins G, A and M, anti-HBs was determined. RESULTS The tests showed that 11% of patients presented IgG levels below the age related reference values. Children with reduced IgG concentration were also found to have significantly lower vitamin D concentrations in comparison to children with normal IgG. Vitamin D deficiency was observed in schoolchildren between 7 and 18 years of age. No correlation was found between 25(OH)D concentration and Hbs antibody levels. CONCLUSIONS An investigation of a large group of patients who have recurrent infection found patients with IgG deficiency to whom special proceeding have to be performed: 1. Significantly lower vitamin D concentration observed in the group of children with IgG deficiency implicated in long-lasting monitoring of vitamin D level require adding to the practice guidelines for Central Europe 2013. 2. Intervention treatment with suitable doses of vitamin D to clarified metabolism of vitamin D has to be plan for children with IgG deficiency and significant lower vitamin D concentration.
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14
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Abstract
Vitamin D metabolism is complex and its deficiency has proven to be deleterious in bone health, and to have significant effects on the immune and cardiovascular systems. Vitamin D has also been associated with pulmonary diseases outcomes. This review will focus on vitamin D metabolism, and studies performed mostly in children with asthma or Cystic Fibrosis.
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Affiliation(s)
- Sofia Konstantinopoulou
- Division of Pulmonary Medicine, Sheikh Khalyfa Medical City, Al Karama Street, Tibbiyya, Abu Dhabi, United Arab Emirates
| | - Ignacio E Tapia
- Perelman School of Medicine at the University of Pennsylvania, Sleep Center, Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, USA.
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15
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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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16
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Tangpricha V, Smith EM, Binongo J, Judd SE, Ziegler TR, Walker S, Tirouvanziam R, Zughaier SM, Lee MJ, Chesdachai S, Hermes WA, Chmiel JF, Gaggar A, Grossmann RE, Joseph PM, Alvarez JA. The Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC) trial: Rationale and design of a multi-center, double-blind, placebo-controlled trial of high dose bolus administration of vitamin D3 during acute pulmonary exacerbation of cystic fibrosis. Contemp Clin Trials Commun 2017; 6:39-45. [PMID: 28508087 PMCID: PMC5427007 DOI: 10.1016/j.conctc.2017.02.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2016] [Revised: 01/31/2017] [Accepted: 02/28/2017] [Indexed: 12/30/2022] Open
Abstract
Vitamin D deficiency is highly prevalent in children and adults with cystic fibrosis (CF). Recent studies have found an association between vitamin D status and risk of pulmonary exacerbations in children and adults with CF. The ongoing Vitamin D for enhancing the Immune System in Cystic fibrosis (DISC) study is a multi-center, double-blind, randomized, placebo-controlled trial that will test the hypothesis of whether high dose vitamin D given as a single oral bolus of 250,000 IU to adults with CF during a pulmonary exacerbation followed by a maintenance dose of vitamin D will improve time to next pulmonary exacerbation and re-hospitalization, improve survival and lung function compared to placebo and reduce the rates of pulmonary exacerbation,. Subjects will be randomized 1:1 at each clinical site to vitamin D or placebo within 72 hours of hospital admission for pulmonary exacerbation. Clinical follow-up visits will occur at 1, 2, 3, and 7 days, and 1, 3, 6 and 12 months after randomization. Blood and sputum will be collected and determination of clinical outcomes will be assessed at each visit. The primary endpoint will be the time to next pulmonary exacerbation requiring antibiotics, re-hospitalization or death. The secondary endpoints will include lung function assessed by forced expiratory volume in 1 second (FEV1), blood markers of inflammatory cytokines, anti-microbial peptide expression by peripheral blood mononuclear cells and circulating concentrations in blood. Other exploratory endpoints will examine the phenotype of neutrophils and monocyte/macrophages in sputum. Nutritional status will be assessed by 3 day food records and food frequency questionnaire.
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Affiliation(s)
- Vin Tangpricha
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA, United States
- Atlanta VA Medical Center, Decatur, GA, United States
- Nutrition Health Sciences Program, Emory University School of Public Health, Emory University, Atlanta, GA, United States
| | - Ellen M. Smith
- Nutrition Health Sciences Program, Emory University School of Public Health, Emory University, Atlanta, GA, United States
| | - Jose Binongo
- Department of Biostatistics, Emory University School of Public Health, Emory University, Atlanta, GA, United States
| | - Suzanne E. Judd
- Department of Biostatistics, The University of Alabama at Birmingham, Birmingham, AL, United States
| | - Thomas R. Ziegler
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA, United States
- Atlanta VA Medical Center, Decatur, GA, United States
- Nutrition Health Sciences Program, Emory University School of Public Health, Emory University, Atlanta, GA, United States
| | - Seth Walker
- Division of Pulmonary Medicine and Critical Care, Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States
| | - Rabindra Tirouvanziam
- Division of Pulmonology, Allergy, Cystic Fibrosis and Sleep, Department of Pediatrics, Center for CF and Airways Disease Research, Emory University School of Medicine, Atlanta, GA, United States
| | - Susu M. Zughaier
- Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States
| | - Moon Jeong Lee
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA, United States
- Atlanta VA Medical Center, Decatur, GA, United States
| | - Supavit Chesdachai
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA, United States
- Atlanta VA Medical Center, Decatur, GA, United States
| | - Wendy A. Hermes
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA, United States
- Atlanta VA Medical Center, Decatur, GA, United States
- Georgia State University, Byrdine F. Lewis School of Nursing and Health Professionals, Atlanta, GA, United States
| | - James F. Chmiel
- University Hospitals Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Amit Gaggar
- Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, The University of Alabama at Birmingham and Birmingham VA Medical Center, Birmingham, AL, United States
| | - Ruth E. Grossmann
- College of Nursing, University of Iowa, Iowa City, IA, United States
| | - Patricia M. Joseph
- Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
| | - Jessica A. Alvarez
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA, United States
- Atlanta VA Medical Center, Decatur, GA, United States
- Nutrition Health Sciences Program, Emory University School of Public Health, Emory University, Atlanta, GA, United States
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17
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Pincikova T, Paquin-Proulx D, Sandberg JK, Flodström-Tullberg M, Hjelte L. Vitamin D treatment modulates immune activation in cystic fibrosis. Clin Exp Immunol 2017; 189:359-371. [PMID: 28470739 DOI: 10.1111/cei.12984] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/19/2017] [Indexed: 12/11/2022] Open
Abstract
Persistent inflammatory response in cystic fibrosis (CF) airways is believed to play a central role in the progression of lung damage. Anti-inflammatory treatment may slow lung disease progression, but adverse side effects have limited its use. Vitamin D has immunoregulatory properties. We randomized 16 CF patients to receive vitamin D2, vitamin D3 or to serve as controls, and investigated the effect of vitamin D supplementation on soluble immunological parameters, myeloid dendritic cells (mDCs) and T cell activation. Three months of vitamin D treatment were followed by two washout months. Vitamin D status at baseline was correlated negatively with haptoglobin, erythrocyte sedimentation rate and immunoglobulin A concentration. Total vitamin D dose per kg bodyweight correlated with the down-modulation of the co-stimulatory receptor CD86 on mDCs. Vitamin D treatment was associated with reduced CD279 (PD-1) expression on CD4+ and CD8+ T cells, as well as decreased frequency of CD8+ T cells co-expressing the activation markers CD38 and human leucocyte antigen D-related (HLA-DR) in a dose-dependent manner. There was a trend towards decreased mucosal-associated invariant T cells (MAIT) cell frequency in patients receiving vitamin D and free serum 25-hydroxyvitamin D (free-s25OHD) correlated positively with CD38 expression by these cells. At the end of intervention, the change in free-s25OHD was correlated negatively with the change in CD279 (PD-1) expression on MAIT cells. Collectively, these data indicate that vitamin D has robust pleiotropic immunomodulatory effects in CF. Larger studies are needed to explore the immunomodulatory treatment potential of vitamin D in CF in more detail.
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Affiliation(s)
- T Pincikova
- Stockholm CF Center, Karolinska University Hospital Huddinge, Stockholm, Sweden.,Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.,Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - D Paquin-Proulx
- Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - J K Sandberg
- Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - M Flodström-Tullberg
- Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - L Hjelte
- Stockholm CF Center, Karolinska University Hospital Huddinge, Stockholm, Sweden.,Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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18
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Alvarez JA, Chong EY, Walker DI, Chandler JD, Michalski ES, Grossmann RE, Uppal K, Li S, Frediani JK, Tirouvanziam R, Tran VT, Tangpricha V, Jones DP, Ziegler TR. Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D 3 administration. Metabolism 2017; 70:31-41. [PMID: 28403943 PMCID: PMC5407388 DOI: 10.1016/j.metabol.2017.02.006] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 01/07/2017] [Accepted: 02/05/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. OBJECTIVE We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. DESIGN Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3 (250,000IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs. deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3 supplementation. RESULTS Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways-predominantly representing amino acid pathways-differed between the vitamin D3- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D3 treatment. CONCLUSIONS Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D3 in this clinical setting.
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Affiliation(s)
- Jessica A Alvarez
- Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA.
| | - Elizabeth Y Chong
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Douglas I Walker
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Joshua D Chandler
- Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Ellen S Michalski
- Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Nutrition and Health Sciences Graduate Program, Laney Graduate School, Emory University, Atlanta, GA, USA
| | | | - Karan Uppal
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Shuzhao Li
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Jennifer K Frediani
- Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Nutrition and Health Sciences Graduate Program, Laney Graduate School, Emory University, Atlanta, GA, USA
| | - Rabindra Tirouvanziam
- Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Division of Pulmonary, Allergy & Immunology, Cystic Fibrosis and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - ViLinh T Tran
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Vin Tangpricha
- Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Section of Endocrinology, Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA
| | - Dean P Jones
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Thomas R Ziegler
- Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Center for Cystic Fibrosis and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, USA; Section of Endocrinology, Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA
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19
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Pincikova T, Paquin-Proulx D, Sandberg JK, Flodström-Tullberg M, Hjelte L. Clinical impact of vitamin D treatment in cystic fibrosis: a pilot randomized, controlled trial. Eur J Clin Nutr 2016; 71:203-205. [DOI: 10.1038/ejcn.2016.259] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 10/24/2016] [Accepted: 10/26/2016] [Indexed: 12/21/2022]
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20
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Coriati A, Labrèche É, Mailhot M, Mircescu H, Berthiaume Y, Lavoie A, Rabasa-Lhoret R. Vitamin D 3 supplementation among adult patients with cystic fibrosis. Clin Nutr 2016; 36:1580-1585. [PMID: 27769784 DOI: 10.1016/j.clnu.2016.10.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Revised: 05/24/2016] [Accepted: 10/04/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Vitamin D (Vit D) deficiency in cystic fibrosis (CF) is partially secondary to exocrine pancreatic insufficiency. Our aim was to establish a Vit D3 supplementation protocol that will increase 25(OH)D to the recommended level (30 ng/mL). METHODS Retrospective study of 200 patients (≥18 years) conducted from February 2007 to June 2014 at the CF clinic of the Centre Hospitalier de l'Université de Montréal. Vit D3 supplementation protocol was 1600 IU/day or 10,000 IU/week during the summer (May 1st to October 31st) and 3200 IU/day or 20,000 IU/week during the winter (November 1st to April 30th), in addition to the 1200 IU/day included in multivitamins. RESULTS Significant increase in serum 25(OH)D levels from baseline (25.9 ± 10.3 ng/mL) to follow-up (37.0 ± 11.4 ng/mL) (P ≤ 0.001). At follow-up, increased doses during the winter improved serum 25(OH)D levels to a degree comparable to the summer. CONCLUSIONS This supplementation protocol is efficient and needs to be tested in other CF adult cohorts and correlated to potential health benefit measurements.
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Affiliation(s)
- Adèle Coriati
- Institut de recherches cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada; Department of Nutrition, Université de Montréal, Montréal, Québec, H3T 1A8, Canada
| | - Évelyne Labrèche
- Institut de recherches cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada; Department of Medicine, Université de Montréal, Montréal, Québec, H3T 1J4, Canada
| | - Marjolaine Mailhot
- Cystic Fibrosis Clinic of the Centre Hospitalier de l'Université de Montréal, Montréal, Québec, H2W 1T8, Canada
| | - Hortensia Mircescu
- Department of Medicine, Université de Montréal, Montréal, Québec, H3T 1J4, Canada; Cystic Fibrosis Clinic of the Centre Hospitalier de l'Université de Montréal, Montréal, Québec, H2W 1T8, Canada
| | - Yves Berthiaume
- Institut de recherches cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada; Department of Medicine, Université de Montréal, Montréal, Québec, H3T 1J4, Canada; Cystic Fibrosis Clinic of the Centre Hospitalier de l'Université de Montréal, Montréal, Québec, H2W 1T8, Canada
| | - Annick Lavoie
- Cystic Fibrosis Clinic of the Centre Hospitalier de l'Université de Montréal, Montréal, Québec, H2W 1T8, Canada
| | - Rémi Rabasa-Lhoret
- Institut de recherches cliniques de Montréal, Montréal, Québec, H2W 1R7, Canada; Department of Nutrition, Université de Montréal, Montréal, Québec, H3T 1A8, Canada; Department of Medicine, Université de Montréal, Montréal, Québec, H3T 1J4, Canada; Cystic Fibrosis Clinic of the Centre Hospitalier de l'Université de Montréal, Montréal, Québec, H2W 1T8, Canada.
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Shahin WA, Hamed DHED, El enbaby NAM, Sharaf SAE, Mahmoud RAK, El-Falaki MM. Vitamin D and its binding protein in children with cystic fibrosis: A single center study. EGYPTIAN PEDIATRIC ASSOCIATION GAZETTE 2016. [DOI: 10.1016/j.epag.2016.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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Coriati A, Lehoux Dubois C, Phaneuf M, Mailhot M, Lavoie A, Berthiaume Y, Rabasa-Lhoret R. Relationship between vitamin D levels and glucose tolerance in an adult population with cystic fibrosis. DIABETES & METABOLISM 2016; 42:135-8. [DOI: 10.1016/j.diabet.2015.11.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2015] [Accepted: 11/05/2015] [Indexed: 11/16/2022]
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Vitamin D deficiency is associated with pulmonary dysfunction in cystic fibrosis. J Cyst Fibros 2015; 14:497-506. [DOI: 10.1016/j.jcf.2014.12.006] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Revised: 12/05/2014] [Accepted: 12/11/2014] [Indexed: 11/22/2022]
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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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Abstract
BACKGROUND Observational studies have linked vitamin D status and infectious disease. This association is supported by the presence of the vitamin D receptor and CYP27B1 in immune cells. This review aims to consolidate data from clinical trials that used vitamin D for the treatment or prevention of infectious disease. METHODS The authors searched the term "(vitamin D OR ergocalciferol OR cholecalciferol OR vitamin D2 OR vitamin D3 OR calcitriol) AND (infection OR tuberculosis OR sepsis OR pneumonia)" with limits preset to manuscripts published in English and with human subjects. They identified controlled trials that measured infectious outcomes (eg, incidence and severity of disease, time to disease resolution or recurrence, measures of clinical improvement, mortality). Studies that used analog, topical or micronutrient formulations of vitamin D, assessed only vitamin D status or lacked a comparison group were excluded. The references from eligible manuscripts and from 2 recent reviews were scanned for additional manuscripts. RESULTS One thousand two hundred eighty-four manuscripts were identified with our search terms, with 60 papers still eligible after review of the title and abstract. Full review of these papers, their references and 2 related reviews yielded 38 manuscripts. CONCLUSIONS Although some prospective studies show positive results regarding vitamin D on infectious disease, several robust studies are negative. Factors such as high variability between studies, the difference in individual responsiveness to vitamin D and study designs that do not primarily investigate infectious outcomes may mask the effects of vitamin D on infections.
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Vanstone MB, Egan ME, Zhang JH, Carpenter TO. Association between serum 25-hydroxyvitamin D level and pulmonary exacerbations in cystic fibrosis. Pediatr Pulmonol 2015; 50:441-6. [PMID: 25657016 DOI: 10.1002/ppul.23161] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 11/16/2014] [Accepted: 11/30/2014] [Indexed: 01/17/2023]
Abstract
OBJECTIVE To identify effects of vitamin D status, as defined by circulating 25-hydroxyvitamin D (25-OHD) levels on the annual frequency of pulmonary exacerbations (Pex) and hospitalizations, on standard measures of pulmonary function, and to identify determinants of 25-OHD levels in pediatric patients with cystic fibrosis (CF). HYPOTHESIS Higher levels of serum 25-OHD would be associated with fewer Pex and hospitalizations, and improved lung function based on pulmonary function tests (PFTs). STUDY DESIGN Retrospective chart review of 53 pediatric patients from January 2011 to December 2011. Significant relationships were examined using linear and logistic regression analyses. PATIENT SELECTION Patients ages 5 through 22 years followed at the CF Care Center and Clinic at Yale-New Haven Hospital, New Haven, CT., who had at least four clinic visits and at least one 25-OHD measurement between January 1, 2011 and December 31, 2011. RESULTS Serum 25-OHD level and gender were strong independent determinants of the annual number of Pex (P < 0.01, with lower 25-OHD level and female gender associated with Pex). There was a significant influence of gender (P < 0.05) and a near-significant influence of serum 25-OHD (P < 0.08) on hospitalization rate. There was no effect of 25-OHD levels on PFTs. Other candidate factors (age, season, gender, pancreatic sufficiency, or severity of genetic mutation) did not significantly effect 25-OHD level. CONCLUSIONS The annual number of Pex in pediatric CF patients is significantly associated with 25-OHD levels and gender, raising the consideration that maintaining vitamin D sufficiency may lead to decreased incidence of Pex and hospitalizations requiring antibiotic therapy.
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Affiliation(s)
- Michelle B Vanstone
- Department of Pediatrics, Sections of Endocrinology, Yale University School of Medicine, New Haven, Connecticut
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Vitamin D status in children with cystic fibrosis. Associations with inflammation and bacterial colonization. Ann Am Thorac Soc 2014; 11:205-10. [PMID: 24423241 DOI: 10.1513/annalsats.201306-171bc] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
RATIONALE Patients with cystic fibrosis (CF) have high rates of vitamin D insufficiency. The relation between vitamin D status and inflammation in patients with CF is poorly understood. OBJECTIVES To determine the prevalence of vitamin D deficiency and insufficiency in a young CF population and to examine correlations between vitamin D status, disease severity, and inflammatory markers. METHODS This was a retrospective chart review of patients with CF under the age of 12 years. Serum laboratory parameters, growth indices, pancreatic status, CFTR genetics, medications, microbiology, and presence of CF-related comorbidities were collected for patients who had fat-soluble vitamin levels measured between January 1, 2009 and December 31, 2011. Vitamin D deficiency was defined as a serum 25(OH)D less than 20 ng/ml and insufficiency as serum 25(OH)D 20 to 29.9 ng/ml. Associations between serum vitamin D concentration and clinical/inflammatory markers were assessed using Chi-square and t tests. MEASUREMENTS AND MAIN RESULTS Data were collected for 148 children. The mean serum 25(OH)D concentration was 32.4 ng/ml (SD, 8.9). Seven percent (10 of 148) were vitamin D deficient, and 36% (53 of 148) were vitamin D insufficient. Among the pancreatic-sufficient patients, 50% (14 of 28) were vitamin D insufficient/deficient, whereas among pancreatic-insufficient patients, 41% (49 of 120) were vitamin D insufficient/deficient. Pseudomonas aeruginosa was a more common pathogen in the patients who were vitamin D insufficient/deficient (18 of 63 vs. 11 of 85, P = 0.018). There was no difference between vitamin D-sufficient versus -insufficient groups in terms of other bacterial colonization or inflammatory markers. CONCLUSIONS Overall, vitamin D insufficiency is common among young children with CF. Vitamin D insufficiency is prevalent even in children who are pancreatic sufficient. In this population, vitamin D insufficiency is associated with a history of Pseudomonas colonization but not with classic markers of systemic inflammation.
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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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Legarda M, Gordon G, Lloyd C, Baumann U, Kelly DA, Shaw N, McKiernan P. Vitamin D deficiency and insufficiency after pediatric liver transplantation. Pediatr Transplant 2013; 17:631-7. [PMID: 23962009 DOI: 10.1111/petr.12135] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/11/2013] [Indexed: 01/08/2023]
Abstract
Vitamin D deficiency and insufficiency are increasingly recognized in the general population, including healthy children. There is also an increasing emphasis on the importance of vitamin D status following pediatric liver transplantation and specifically its relationship to metabolic bone disease and growth retardation. Vitamin D insufficiency has also been associated with multiple immunological and metabolic disorders in adults. To our knowledge, this has not been systematically evaluated in children undergoing liver transplantation to date. Between October 2004 and August 2008, serum 25-(OH)-vitamin D levels were measured in 199 children who had undergone liver transplantation at Birmingham Children's Hospital. Potential factors contributing to vitamin D levels were evaluated. Additionally, we evaluated a possible relationship between vitamin D levels and immunological phenomena and metabolic complications. Median 25-(OH)-vitamin D level was 19.5 ng/mL (range: 4.4-71.4 ng/mL). A total of 105 children (53%) had insufficient vitamin D levels and 28 children (14%) showed vitamin D deficiency. The only factors found to be associated with vitamin D deficiency were season of sample, ethnicity, and PTH levels. Vitamin D deficiency was more prevalent during the first year after transplantation. We did not find a significant relationship between vitamin D levels and graft function or any other immunological and metabolic complications. Vitamin D insufficiency and deficiency are common in children after liver transplantation, especially in winter and spring and in non-white patients. Initial post-transplant period and high PTH are significantly associated with vitamin D deficiency. Vitamin D status should be monitored following pediatric liver transplantation and vitamin D supplementation provided as required.
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Affiliation(s)
- Maria Legarda
- Liver Unit, Birmingham Children's Hospital, Birmingham, UK
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Hu J, Luo Z, Zhao X, Chen Q, Chen Z, Qin H, Qin Y, Liang X, Suo Y. Changes in the calcium-parathyroid hormone-vitamin d axis and prognosis for critically ill patients: a prospective observational study. PLoS One 2013; 8:e75441. [PMID: 24073266 PMCID: PMC3779172 DOI: 10.1371/journal.pone.0075441] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Accepted: 08/15/2013] [Indexed: 01/07/2023] Open
Abstract
OBJECTIVE Vitamin D deficiency is prevalent in critically ill patients and may contribute to suboptimal clinical outcomes, but little is known about alterations of the calcium-parathyroid hormone (PTH)-vitamin D axis and prognosis in these individuals. METHODS A prospective observational study was conducted on 216 patients admitted to a university-affiliated, tertiary-care medical intensive care unit(MICU) between June 2011 and December 2012. Serum levels of 25-hydroxyvitamin D, ionised calcium and intact PTH were determined within 24 h of MICU admission. The primary end point was all-cause hospital mortality within 90-days of admission. RESULTS 95 patients (44%) showed 25-hydroxyvitamin D deficiency. Patients deficient in vitamin D showed significantly higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, rate of positive blood culture, incidence of multiple organ dysfunction syndrome, and 90-day mortality rate than did patients with vitamin D insufficiency or sufficiency (P<0.05), as well as lower levels of serum IgG. 25-Hydroxyvitamin D deficiency was identified as an independent risk factor for mortality (OR = 3.018, 95%CI 1.329-6.854, P = 0.008). Hypovitaminosis D in PTH-responders was associated with higher mortality than was the same condition in non-responders (P<0.05). CONCLUSIONS These results suggest that vitamin D deficiency is prevalent among MICU patients, suggesting a significant derangement of the calcium-PTH-vitamin D axis in critically ill patients. Vitamin D deficiency is an independent risk factor for 90-day mortality, and hypovitaminosis D in PTH-responders is associated with higher mortality than is the same condition in non-responders.
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Affiliation(s)
- Jieyu Hu
- Intensive Care Unit, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zuojie Luo
- Department of Endocrinology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiaoqin Zhao
- Intensive Care Unit, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Qiang Chen
- Intensive Care Unit, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhaoyan Chen
- Intensive Care Unit, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hua Qin
- Intensive Care Unit, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yingfen Qin
- Department of Endocrinology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xinghuan Liang
- Department of Endocrinology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yingjun Suo
- Department of Endocrinology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Papadimitriou DT, Marakaki C, Fretzayas A, Nicolaidou P, Papadimitriou A. Negativation of type 1 diabetes-associated autoantibodies to glutamic acid decarboxylase and insulin in children treated with oral calcitriol. J Diabetes 2013; 5:344-348. [PMID: 23302101 DOI: 10.1111/1753-0407.12023] [Citation(s) in RCA: 16] [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: 10/28/2012] [Revised: 12/16/2012] [Accepted: 12/19/2012] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Based on recent knowledge of the possible involvement of 1,25-dihydroxyvitamin D in the pathogenesis of type 1 diabetes (T1D) and the results of its administration in animal models, we conducted a clinical trial by treating high-risk children, positive for T1D autoantibodies, with oral calcitriol. METHODS The present prospective trial was performed on 12 children (1.5-13 years old) who were investigated for the potential risk of T1D because of an already diagnosed association of celiac disease and autoimmune thyroiditis (four girls), autoimmune thyroiditis at a very young age (two girls, two boys), a diagnosis of T1D in siblings (two boys), and impaired glucose tolerance (IGT; one boy, one girl). Serum autoantibody levels, including islet cell autoantibodies, anti-glutamic acid decarboxylase (GAD) 65, insulin autoantibodies (IAA), and anti-tyrosine phosphatase, and markers of calcium metabolism were evaluated prior to and at 6-monthly intervals after the initiation of 0.25 μg/day calcitriol for 1-3 years. RESULTS In all children, persistent negativation of the anti-GAD65 antibodies and IAA was observed within 0.4-2.1 years. Of the two children with IGT, the boy proved to have maturity onset diabetes of the young (MODY) 2, whereas the glycemic profile was normalized in the girl. CONCLUSIONS Despite the small number of subjects and the absence of a control group in the present study, 0.25 μg/day calcitriol effectively negativates anti-GAD65 antibodies and IAA after a median time of 6 months. This simple, safe, and low-cost strategy may prove effective in the prevention of T1D in the future.
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Sakem B, Nock C, Stanga Z, Medina P, Nydegger UE, Risch M, Risch L. Serum concentrations of 25-hydroxyvitamin D and immunoglobulins in an older Swiss cohort: results of the Senior Labor Study. BMC Med 2013; 11:176. [PMID: 23902738 PMCID: PMC3751655 DOI: 10.1186/1741-7015-11-176] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Accepted: 07/22/2013] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Vitamin D and the components of humoral immunity play important roles in human health. Older people have lower 25-hydroxyvitamin D (25(OH)D) serum levels than younger adults. We aimed to determine the levels of 25(OH)D serum concentrations in healthy senior citizens and to study their relationship to the levels of components of humoral immunity. METHODS A total of 1,470 healthy Swiss men and women, 60 years or older, were recruited for this study. A total of 179 subjects dropped out of the study because of elevated serum concentrations of C-reactive protein. Fasting blood sera were analyzed for 25(OH)D with the high-performance liquid chromatography (HPLC) and for parathyroid hormone (PTH), immunoglobulins and complement C4 and C3 concentrations with immunoassays. The percentage of participants in each of the four 25(OH)D deficiency groups--severely deficient (<10 ng/ml), deficient (10 to 20), insufficient (21 to 29 ng/ml) and normal (>=30 ng/ml)--were statistically compared. The relationship of the major components of the humoral system and age with 25(OH)D levels was also assessed. RESULTS About 66% of the subjects had insufficient levels of 25(OH)D. Normal levels of 25(OH)D were found in 26.1% of the subjects of which 21% were males and 30.5% were females (total study population). Severely deficient levels of 25(OH)D were found in 7.98% of the total study population. Low levels of 25(OH)D were positively associated with IgG2 (P = 0.01) and with C4 (P = 0.02), yet were inversely related to levels of IgG1 and IgA (P < 0.05) and C3 (P = 0.01). Serum levels of total IgA, IgG, IgG2 and IgG4 peaked together with 25(OH)D during late summer. CONCLUSIONS Approximately two-thirds of the healthy, older Swiss population presented with Vitamin D insufficiency. The incremental shift in IgA and C3 levels might not necessarily reflect a deranged humoral immune defense; however, given the high prevalence of vitamin D deficiency, the importance of this condition in humoral immunity will be worth looking at more closely. This study supports the role of vitamin D in the competent immune system.
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Affiliation(s)
- Benjamin Sakem
- Division of Clinical Chemistry, Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, CH-3097, Liebefeld bei Bern, Switzerland
| | - Cristina Nock
- Private Medical Office, Grundgasse 2, CH-6460, Altdorf, Switzerland
| | - Zeno Stanga
- Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Bern, Switzerland
- Division of General Internal Medicine, University Hospital, Bern, Switzerland
| | - Pedro Medina
- Division of Clinical Chemistry, Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, CH-3097, Liebefeld bei Bern, Switzerland
| | - Urs E Nydegger
- Division of Clinical Chemistry, Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, CH-3097, Liebefeld bei Bern, Switzerland
| | - Martin Risch
- Central Laboratory, Kantonsspital Graubünden, Chur, Switzerland
| | - Lorenz Risch
- Division of Clinical Chemistry, Labormedizinisches Zentrum Dr. Risch, Waldeggstrasse 37, CH-3097, Liebefeld bei Bern, Switzerland
- Private University of the Principality of Liechtenstein, Triesen, Principality of Liechtenstein
- Division of Clinical Biochemistry Medical University Innsbruck, Innsbruck, Austria
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Ryoo E, Kumar R, Kita H, Juhn YJ. Serum 25-hydroxyvitamin D concentrations and waning pneumococcal antibody titers among individuals with atopy. Allergy Asthma Proc 2013; 34:370-7. [PMID: 23883602 PMCID: PMC5554329 DOI: 10.2500/aap.2013.34.3656] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Serum 25-hydroxyvitamin D (25[OH]D) concentrations are positively associated with pneumococcal antibody titers (PATs) in subjects with atopy or asthma. Little is known about the association of serum 25(OH)D concentrations and the waning of PATs over time in subjects with or without atopy. This study was designed to determine whether serum 25(OH)D concentrations are associated with waning of PATs and if such relationship is modified by atopic conditions. The study was designed as a prospective cohort study, which followed 20 asthmatic patients and 19 individuals without asthma for an average of 12 months. We measured PATs and serum 25(OH)D concentrations at baseline and at a subsequent follow-up visit. Asthma was ascertained by predetermined criteria. The association between serum 25(OH)D concentrations and PATs was determined by Pearson's correlation coefficient and a least square model. Of the 39 children and adults, 21(53%) were male subjects, all were white, and 6 (15%) were children. There was an overall negative correlation between serum 25(OH)D concentrations and the decrease of PATs during follow-up (r = -0.47; p = 0.004), suggesting that higher 25(OH)D concentrations were associated with a reduction in waning of PATs over time. Controlling for follow-up duration and pneumococcal colonization, these trends were significant among asthmatic patients but not in individuals without asthma. Similar trends were observed for individuals with or without other atopic conditions. Serum 25(OH)D concentrations are inversely associated with the waning of PATs over time, especially individuals with asthma and other atopy conditions. These study findings deserve further investigation.
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Affiliation(s)
- Eell Ryoo
- Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA
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Bartley J, Garrett J, Grant CC, Camargo CA. Could vitamin d have a potential anti-inflammatory and anti-infective role in bronchiectasis? Curr Infect Dis Rep 2013; 15:148-57. [PMID: 23371406 DOI: 10.1007/s11908-013-0321-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Bronchiectasis is a chronic infective and inflammatory respiratory disease that causes significant morbidity and mortality. Patients with non-cystic-fibrosis bronchiectasis are frequently vitamin D deficient, and vitamin D levels correlate with disease severity. Infection-specific actions of vitamin D include the enhancement of innate immunity and the moderation of inflammation caused by the adaptive immune response. Potentially, vitamin D could influence the processes that lead to bronchiectasis and the frequency and severity of acute exacerbations. Randomized trials of vitamin D supplementation have shown effects that are likely to be protective against the development of bronchiectasis. Several issues need to be clarified before the development of clinical trials to investigate the role of vitamin D in bronchiectasis. These include an optimal vitamin D supplementation dose and appropriate and sensitive outcome measures that include assessment of exacerbation frequency and severity, lung function, and health-related quality of life.
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Affiliation(s)
- Jim Bartley
- Department of Surgery, University of Auckland, 10 Owens Road, Auckland, 1023, New Zealand,
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Grossmann RE, Zughaier SM, Kumari M, Seydafkan S, Lyles RH, Liu S, Sueblinvong V, Schechter MS, Stecenko AA, Ziegler TR, Tangpricha V. Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation: A randomized, controlled trial. DERMATO-ENDOCRINOLOGY 2012; 4:191-7. [PMID: 22928076 PMCID: PMC3427199 DOI: 10.4161/derm.20332] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
<u>Background:</u> Vitamin D insufficiency is common in cystic fibrosis (CF) and vitamin D repletion may have an important role in improving clinical outcomes in CF. This randomized, placebo-controlled, pilot study examined the feasibility and impact of a single, large dose of cholecalciferol on vitamin D status and clinical outcomes in subjects with CF.
<u>Methods:</u> Thirty adults with were randomized in a double-blinded, pilot study to receive 250,000 IU cholecalciferol or placebo within 48 h of hospital admission for a pulmonary exacerbation. Concentrations of 25-hydroxyvitamin D (25(OH)D), clinical outcomes and potential adverse events were assessed up to one year after randomization. Mixed effects linear regression models were used to evaluate the difference in mean serum concentrations and log-rank analyses were used to evaluate survival.
<u>Results:</u> Data from all subjects was analyzed. Serum 25(OH)D concentrations increased from a mean of 30.6 ± 3.2 ng/mL to 58.1 ± 3.5 ng/mL (p < 0.001) at one week and 36.7 ± 2.6 ng/mL by 12 weeks (p = 0.06) in the vitamin D group; in contrast, serum 25(OH)D concentrations remained unchanged in the placebo group. Unadjusted, one-year survival and hospital-free days were increased in the vitamin D group (p = 0.029, p = 0.036; respectively). There was also a trend toward increased IV antibiotic therapy-free days in the vitamin D group (p = 0.073). There were no signs of hypervitaminosis D or adverse events. Serum PTH and calcium concentrations were similar across both groups.
<u>Conclusions:</u> In this pilot study, a single, oral bolus of cholecalciferol increased serum 25(OH)D concentrations and was associated with a trend toward improved clinical outcomes in CF subjects hospitalized for a pulmonary exacerbation. Further investigation is needed into the clinical impact of improved vitamin D status in patients with CF.
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Abstract
OBJECTIVE To review the current literature regarding vitamin D insufficiency and supplementation in major illnesses. DESIGN AND METHODS We reviewed Pubmed-indexed, English language manuscripts from January, 2003 to June, 2012 using search terms related to vitamin D, all-cause mortality, cardiovascular disease, pulmonary disease, diabetes mellitus, and cancer. OUTCOME MEASURES Incidence of disease, risk ratios associated with 25-hydroxyvitamin D [25(OH)D] levels, and/or vitamin D supplementation schedules were documented. RESULTS Although 25(OH)D levels ≥20 ng/mL were often associated with improved health outcomes, evidence suggests that 25(OH)D levels ≥30 ng/mL may confer additional health benefits. CONCLUSIONS Based on the available evidence, vitamin D supplementation to restore 25(OH)D levels within a range of 30-50 ng/mL is reasonable in order to optimize potential benefits and minimize potential risks. This, of course, should be considered in the context of individual patient needs and co-morbidities.
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Affiliation(s)
- Sadeq A Quraishi
- Vitamin D In Stress (ViDIS) Laboratory, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, 5 Fruit Street, GRJ 402, Boston, MA 02114, USA,
| | - Carlos A Camargo
- Emergency Medicine Network (EMNet) Coordinating Center, Department of Emergency Medicine, Massachusetts General Hospital, 326 Cambridge St, Suite 410, Boston, MA 02114,
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Grossmann RE, Zughaier SM, Liu S, Lyles RH, Tangpricha V. Impact of vitamin D supplementation on markers of inflammation in adults with cystic fibrosis hospitalized for a pulmonary exacerbation. Eur J Clin Nutr 2012; 66:1072-4. [PMID: 22805498 PMCID: PMC3638806 DOI: 10.1038/ejcn.2012.82] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Revised: 06/07/2012] [Accepted: 06/08/2012] [Indexed: 12/20/2022]
Abstract
Patients with cystic fibrosis (CF) suffer from chronic lung infection and inflammation leading to respiratory failure. Vitamin D deficiency is common in patients with CF, and correction of vitamin D deficiency may improve innate immunity and reduce inflammation in patients with CF. We conducted a double-blinded, placebo-controlled, randomized clinical trial of high-dose vitamin D to assess the impact of vitamin D therapy on antimicrobial peptide concentrations and markers of inflammation. We randomized 30 adults with CF hospitalized with a pulmonary exacerbation to 250,000 IU of cholecalciferol or placebo, and evaluated changes in plasma concentrations of inflammatory markers and the antimicrobial peptide LL-37 at baseline and 12 weeks post intervention. In the vitamin D group, there was a 50.4% reduction in tumor necrosis factor-α (TNF-α) at 12 weeks (P<0.01), and there was a trend for a 64.5% reduction in interleukin-6 (IL-6) (P=0.09). There were no significant changes in IL-1β, IL-8, IL-10, IL-18BP and NGAL (neutrophil gelatinase-associated lipocalin). We conclude that a large bolus dose of vitamin D is associated with reductions in two inflammatory cytokines, IL-6 and TNF-α. This study supports the concept that vitamin D may help regulate inflammation in CF, and that further research is needed to elucidate the potential mechanisms involved and the impact on clinical outcomes.
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Affiliation(s)
- RE Grossmann
- Nutrition Health Sciences Program, Emory Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA, USA
| | - SM Zughaier
- Division of Pulmonology, Allergy/ Immunology, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
- Center for Cystic Fibrosis Research, Children’s Healthcare of Atlanta, Atlanta, GA, USA
| | - S Liu
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - RH Lyles
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - V Tangpricha
- Nutrition Health Sciences Program, Emory Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA, USA
- Center for Cystic Fibrosis Research, Children’s Healthcare of Atlanta, Atlanta, GA, USA
- Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
- Staff Physician, Atlanta VA Medical Center, Atlanta, GA, USA
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Holmøy T, Lossius A, Gundersen TE, Moen SM, Castellazzi M, Fainardi E, Casetta I. Intrathecal levels of vitamin D and IgG in multiple sclerosis. Acta Neurol Scand 2012; 125:e28-31. [PMID: 21781056 DOI: 10.1111/j.1600-0404.2011.01577.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Intrathecal synthesis of IgG is a hallmark of multiple sclerosis (MS). Vitamin D may modulate B-cell function and dampen the synthesis of IgG. OBJECTIVE To investigate the relation between vitamin D levels in cerebrospinal fluid and serum and intrathecal synthesis of IgG. METHODS 25-hydroxyvitamin D (25(OH)D) and IgG were assessed in cerebrospinal fluid and serum in 40 patients with MS. RESULTS There was no significant correlation between the IgG index and 25(OH)D levels in cerebrospinal fluid or serum. The levels of 25(OH)D in cerebrospinal fluid and serum did not differ between patients with and without intrathecal synthesis of IgG. There was a non-significant trend towards a positive correlation between the concentrations of 25(OH)D and IgG in the cerebrospinal fluid, but not in serum. CONCLUSION Physiological variation in vitamin D does not exert a major impact on intrathecal synthesis of IgG in MS.
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Affiliation(s)
- T Holmøy
- Department of Neurology, Akershus University Hosptital, Lørenskog, Norway.
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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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Current world literature. Curr Opin Pediatr 2012; 24:134-44. [PMID: 22245849 DOI: 10.1097/mop.0b013e328350498a] [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: 11/26/2022]
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Pincikova T, Nilsson K, Moen IE, Fluge G, Hollsing A, Knudsen PK, Lindblad A, Mared L, Pressler T, Hjelte L. Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study. Diabetologia 2011; 54:3007-15. [PMID: 21901282 DOI: 10.1007/s00125-011-2287-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2011] [Accepted: 07/26/2011] [Indexed: 01/05/2023]
Abstract
AIMS/HYPOTHESIS Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis-related glucose intolerance. METHODS We enrolled 898 cystic fibrosis patients from Sweden, Norway and Denmark. Vitamin D intake was assessed using a seven-day food record. Serum 25-hydroxyvitamin D (s25OHD) and HbA(1c) were measured, and an OGTT was carried out. Multiple linear and logistic regressions were used for HbA(1c) and cystic fibrosis-related diabetes/OGTT result as outcome variables, respectively. Each model was controlled for country, and for known cystic fibrosis-related diabetes risk factors: age, sex, genotype, liver dysfunction, long-term corticosteroid treatment, and lung and pancreatic function. RESULTS Degree of vitamin D insufficiency (OR 1.36; p = 0.032) and s25OHD < 30 nmol/l (OR 1.79; p = 0.042) were significant risk factors for cystic fibrosis-related diabetes. Accordingly, HbA(1c) value was positively associated with s25OHD < 30 nmol/l and < 50 nmol/l, as well as with degree of vitamin D insufficiency (adjusted R (2) = 20.5% and p < 0.05 in all). In subgroup analyses, s25OHD < 30 nmol/l determined the HbA(1c) value in paediatric patients (adjusted R (2) = 20.2%; p = 0.017), but not in adults. CONCLUSIONS/INTERPRETATION Vitamin D status is associated with HbA(1c) and diabetes in cystic fibrosis, particularly in children. The study justifies prospective studies on the proposed role of vitamin D deficiency in the pathophysiology of diabetes mellitus.
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Affiliation(s)
- T Pincikova
- Stockholm CF Centre, B 59, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
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Lee J, Zhao H, Fenta Y, Kita H, Kumar R, Juhn YJ. Serum 25-hydroxyvitamin D is associated with enhanced pneumococcal antibody levels in individuals with asthma. Allergy Asthma Proc 2011; 32:445-52. [PMID: 22221439 DOI: 10.2500/aap.2011.32.3494] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Recent studies suggest that vitamin D modulates innate immunity and reduces the risk of microbial infections. Little is known about the role of vitamin D in antipneumococcal immunity in individuals with asthma. We determined the correlation between serum 25-hydroxyvitamin D (25[OH]D) levels and pneumococcal antibody levels in individuals with asthma, atopic dermatitis, or allergic rhinitis, and atopic sensitization status. A cross-sectional study was conducted for 21 subjects with asthma and 23 subjects without asthma. Pearson's correlation coefficient between serum 25(OH)D concentrations and the number of positive serotype-specific antibody levels was calculated among individuals with and without asthma, atopic dermatitis, and/or allergic rhinitis and atopic sensitization status. The overall correlation between serum 25(OH)D concentrations and positive pneumococcal antibody levels in all subjects regardless of asthma was not significant (r = -0.14; p = 0.38). Stratified analysis results showed that there was a positive correlation between serum 25(OH)D concentrations and positive pneumococcal antibody levels in asthmatic patients (r = 0.45; p < 0.05) and an inverse correlation was observed in nonasthmatic patients (r = -0.53; p < 0.05). These trends were similar for subjects with and without atopic dermatitis and/or allergic rhinitis (r = 0.58 and p = 0.008 versus r = -0.63 and p = 0.001). Despite similar trends in the correlation between serum 25(OH)D and pneumococcal antibody concentrations among those with and without atopic sensitization status (r = 0.27 and p = 0.19 versus r = -0.41 and p = 0.08), they did not reach statistical significance. The 25(OH)D may enhance humoral immunity against Streptococcus pneumonia in subjects with atopic conditions but not without atopic conditions. Atopic conditions may have an important effect modifier in the relationship between serum 25(OH)D concentrations and immune function.
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Affiliation(s)
- Jusuk Lee
- Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
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Youssef D, Bailey B, El-Abbassi A, Vannoy M, Manning T, Moorman JP, Peiris AN. Healthcare costs of methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa infections in veterans: role of vitamin D deficiency. Eur J Clin Microbiol Infect Dis 2011; 31:281-6. [PMID: 21695580 DOI: 10.1007/s10096-011-1308-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2011] [Accepted: 05/23/2011] [Indexed: 01/28/2023]
Abstract
Methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) infections are frequently associated with hospitalization and increased healthcare costs. Vitamin D deficiency may contribute to increased costs for patients with these infections and there is evidence that vitamin D may have an antimicrobial role. To evaluate the role of vitamin D deficiency in the costs incurred with these infections, we studied the relationship of serum 25(OH)D levels to healthcare costs in veterans in the southeastern United States. Patients with both infections were vitamin D deficient to a similar extent and so were combined for further analysis. Vitamin D deficient patients had higher costs and service utilization than those who were not vitamin D deficient. Those with vitamin D deficiency had higher inpatient costs compared to the non-deficient group, and this difference was across most categories except for the number of inpatient hospitalizations or total number of days as an inpatient. Vitamin D deficiency was not significantly related to outpatient cost or service utilization parameters. We conclude that vitamin D deficiency is intimately linked to adverse healthcare costs in veterans with MRSA and P. aeruginosa infections. Vitamin D status should be assayed in patients with these infections.
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Affiliation(s)
- D Youssef
- Department of Internal Medicine, Division of Infectious Diseases, East Tennessee State University, Johnson City, TN, USA.
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Finklea JD, Grossmann RE, Tangpricha V. Vitamin D and chronic lung disease: a review of molecular mechanisms and clinical studies. Adv Nutr 2011; 2:244-53. [PMID: 22332056 PMCID: PMC3090167 DOI: 10.3945/an.111.000398] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Vitamin D is classically recognized for its role in calcium homeostasis and skeletal metabolism. Over the last few decades, vitamin D deficiency has increased in prevalence in adults and children. Potential extraskeletal effects of vitamin D have been under investigation for several diseases. Several cross-sectional studies have associated lower vitamin D status with decreased lung function. This finding has prompted investigators to examine the association of vitamin D deficiency with several chronic lung diseases. One major focus has been the link between maternal vitamin D status and childhood asthma. Vitamin D deficiency has also been associated with increased risk of respiratory infection from influenza A and Mycobacterium tuberculosis. Other chronic respiratory diseases associated with vitamin D deficiency include cystic fibrosis, interstitial lung disease, and chronic obstructive pulmonary disease. This review will examine the current clinical literature and potential mechanisms of vitamin D in various pulmonary diseases.
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Affiliation(s)
- James D. Finklea
- Division of Pulmonary, Allergy, and Critical Care Medicine Emory University, Atlanta, GA 30322
| | - Ruth E. Grossmann
- Nutrition and Health Sciences Program, Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322
| | - Vin Tangpricha
- Division of Endocrinology, Diabetes and Lipids, Emory University School of Medicine, Emory University, Atlanta, GA 30322,Nutrition and Health Sciences Program, Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322,Atlanta VA Medical Center, Atlanta, GA 30033,To whom correspondence should be addressed. E-mail:
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