Vitamin D Status of Clinical Practice Populations at Higher Latitudes: Analysis and Applications

Background: Inadequate levels of vitamin D (VTD) throughout the life cycle from the fetal stage to adulthood have been correlated with elevated risk for assorted health afflictions. The purpose of this study was to ascertain VTD status and associated determinants in three clinical practice populationsliving in Edmonton, Alberta, Canada -a locale with latitude of 53°30\u27N, wheresun exposure from October through March is often inadequate to generate sufficient vitamin D. Methods: To determine VTD status, 1,433 patients from three independent medical offices in Edmonton had levels drawn for 25(OH)D as part of their medical assessment between Jun 2001 and Mar 2007. The relationship between demographic data and lifestyle parameters with VTD status was explored. 25(OH)D levels were categorized as follows: (1) Deficient

Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA)

PurposePrevious studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort.MethodsThe levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia.ResultsThe median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004).ConclusionThe results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants

Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial

Funded by Asthma UK grant number 09/ 36

Differential Expression of Cytokines in Response to Respiratory Syncytial Virus Infection of Calves with High or Low Circulating 25-Hydroxyvitamin D3

Deficiency of serum levels of 25-hydroxyvitamin D3 has been related to increased risk of lower respiratory tract infections in children. Respiratory syncytial virus (RSV) is a leading cause of low respiratory tract infections in infants and young children. The neonatal calf model of RSV infection shares many features in common with RSV infection in infants and children. In the present study, we hypothesized that calves with low circulating levels of 25-hydroxyvitamin D3 (25(OH)D3) would be more susceptible to RSV infection than calves with high circulating levels of 25(OH)D3. Calves were fed milk replacer diets with different levels of vitamin D for a 10 wk period to establish two treatment groups, one with high (177 ng/ml) and one with low (32.5 ng/ml) circulating 25(OH)D3. Animals were experimentally infected via aerosol challenge with RSV. Data on circulating 25(OH)D3 levels showed that high and low concentrations of 25(OH)D3 were maintained during infection. At necropsy, lung lesions due to RSV were similar in the two vitamin D treatment groups. We show for the first time that RSV infection activates the vitamin D intracrine pathway in the inflamed lung. Importantly, however, we observed that cytokines frequently inhibited by this pathway in vitro are, in fact, either significantly upregulated (IL-12p40) or unaffected (IFN-γ) in the lungs of RSV-infected calves with high circulating levels of 25(OH)D3. Our data indicate that while vitamin D does have an immunomodulatory role during RSV infection, there was no significant impact on pathogenesis during the early phases of RSV infection. Further examination of the potential effects of vitamin D status on RSV disease resolution will require longer-term studies with immunologically sufficient and deficient vitamin D levels

The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer

The role of vitamin D (VitD) in calcium and bone homeostasis is well described. In the last years, it has been recognized that in addition to this classical function, VitD modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. VitD deficiency appears to be frequent in industrialized countries. Especially patients with lung diseases have often low VitD serum levels. Epidemiological data indicate that low levels of serum VitD is associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases. Several lung diseases, all inflammatory in nature, may be related to activities of VitD including asthma, COPD and cancer. The exact mechanisms underlying these data are unknown, however, VitD appears to impact on the function of inflammatory and structural cells, including dendritic cells, lymphocytes, monocytes, and epithelial cells. This review summarizes the knowledge on the classical and newly discovered functions of VitD, the molecular and cellular mechanism of action and the available data on the relationship between lung disease and VitD status

Vitamin D as an Adjunctive Therapy in Asthma. Part 1: A Review of Potential Mechanisms

Vitamin D deficiency (VDD) is highly prevalent worldwide. The classical role for vitamin D is to regulate calcium absorption form the gastrointestinal tract and influence bone health. Recently vitamin D receptors and vitamin D metabolic enzymes have been discovered in numerous sites systemically supporting diverse extra-skeletal roles of vitamin D, for example in asthmatic disease. Further, VDD and asthma share several common risk factors including high latitude, winter season, industrialization, poor diet, obesity, and dark skin pigmentation. Vitamin D has been demonstrated to possess potent immunomodulatory effects, including effects on T cells and B cells as well as increasing production of antimicrobial peptides (e.g. cathelicidin). This immunomodulation may lead to asthma specific clinical benefits in terms of decreased bacterial/viral infections, altered airway smooth muscle-remodeling and efunction as well as modulation of response to standard anti-asthma therapy (e.g. glucocorticoids and immunotherapy). Thus, vitamin D and its deficiency have a number of biological effects that are potentially important in altering the course of disease pathogenesis and severity in asthma. The purpose of this first of a two-part review is to review potential mechanisms whereby altering vitamin D status may influence asthmatic disease

Vitamin D Deficiency in Children with a Chronic Illness-Seasonal and Age-Related Variations in Serum 25-hydroxy Vitamin D Concentrations

Peer reviewe

Segmental precast prestressd concrete girder design

Bu tez, prekast öngerilmeli segmental tek köprü hücresinin analizi ve tasarımı ile ilgili bilgiler içermektedir. Bu çalışmada, kabloların sonradan germe işlemi, CSI-Bridge yazılımı ve AASHTO LRFD Specified Bridge'e göre yapılmıştır. Geniş açıklıklı, dört şeritli, ön gerilmeli segmental beton köprü tasarımında, değişkenler farklı beton sınıflarının kullanılması, kiriş yüksekliği, kiriş tabanının kalınlığının etkisi, kiriş yan duvarlarının etkişsi ve uygulanan ön gerilme kuvvetlerinin etkisi araştırılmıştır. Bu çalışmada, segmental prekast öngerilmeli beton kirişe en güvenli tasarım modelini elde etmek için farklı kriterlere göre 27 model tasarlanmıştır. Bu kriterler kiriş yüksekliğinin sabit 3 m, veya 3-4,5 m arasında değişken olması, kiriş taban kalınlığının sabit 0.25 m veya 0.25-0.5 m arasında değişken olması, kiriş yan duvarlarının kalınlığının değişik olması, (0.45, 0.5 veya 0.55 m) olması, segmental köprü hücrelerinin üretilmesinde C28, C42 veya C55 sınıfında betonlardan birisinin kullanılması ve bu segmentlerin birbirine montajlarında uygulanan art çekme kuvvetlerinin (3000, 3500, 4000) KN etkisinin kirişlerde oluşacak kesit tesirlerine etkisini araştırılmıştır. Sonuç olarak belirtilen kriterlere göre tasarlanan 27 modelden C55 ve C42 beton kullanılan modellerden çoğunun analizlerinde bu kirişlerin AASHTO LRFD şartnamesinde belirtilen yükleri güvenli olarak taşıyabildiği fakat C28 beton kullanılan modellerin bu şartnamede belirtilen yükleri güvenli bir şekilde taşıyamadığı görülmüştür.This thesis contains information on the analysis and design of the precast pre-stressed concrete segmental single bridge cell. In this structure, post-tensioning of the cable tendon with a large cross-sectional area, four traffic lanes according to AASHTO LRFD Specified, designed the Bridge by CSI-Bridge software, foundations of prestressed concrete, and losses in the pre-tensile strength, wide span, variable depth and resistance to shear force in the web girder, and varying in the thicknesses of bottom slab. In this study 27 models were designed with some different criteria to get the best model of design segmental precast pre-stressed concrete beam, these criteria are depth of girder with constant (3) m and variable (3 – 4.5) m, and the different of the thickness bottom slab (0.25 – 0.5) m, varies the thickness of web girder (0.45, 0.5, 0.55) m, and different value of post-tension tendon stress (3000, 3500, 4000) KN, with the three different concrete grade C28, C42, C55. As a result, in the analysis of 27 models designed according to the specified criteria, C55 and C42 concrete Grade was used, it was observed that these beams could safely carry the loads specified in the AASHTO LRFD specification, but the models using C28, concrete grade could not safely bear the loads specified in this specification

Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y.

OBJECTIVES: To determine whether subclinical vitamin D deficiency in Indian children under 5 y of age is a risk factor for severe acute lower respiratory infection (ALRI). DESIGN: A hospital-based case-control study. SETTING: Sanjeevani Paediatrics Hospital, a private hospital in Indapur, India. PARTICIPANTS: A total of 150 children including 80 cases and 70 controls, aged 2-60 months, were enrolled. Case definition of severe ALRI as given by the World Health Organization was used for cases. Controls were healthy children attending outpatients' service for immunization. MAIN OUTCOME MEASURE: Association of serum 25-hydroxyvitamin D3 (25OHD3) with severe ALRI, controlling for demographic and other potential risk factors. RESULTS: Serum 25OHD3 increased with age. Factors significantly associated with decreased risk of severe ALRI in univariate analysis were: exclusive breastfeeding in the first 4 months (cases 35/78 (45%), controls 41/64 (64%); P=0.02); introduction of other dietary liquids than milk only after 6 months (cases 46/70 (66%), controls 31/66 (47%); P=0.03); use of liquid petroleum cooking fuel (cases 32/80 (40%), controls 40/70 (57%); P=0.04); infant not covered in swaddling cloths when exposed to sunlight before crawling (cases 11/52 (21%), controls 25/54 (46%); P=0.006); and serum 25OHD3>22.5 nmol/l (cases 16/80 (20%), controls 48/70 (69%); P22.5 nmol/l (OR: 0.09; 95% CI 0.03-0.24; P<0.001) and exclusive breastfeeding in the first 4 months of life (OR 0.42; 95% CI 0.18-0.99; P=0.046) with age and height/age as significant covariates. CONCLUSION: Subclinical vitamin D deficiency and nonexclusive breastfeeding in the first 4 months of life were significant risk factors for severe ALRI in Indian children

Effect of vitamin D supplementation of low birth weight term Indian infants from birth on cytokine production at 6 months.

BACKGROUND/OBJECTIVES: Vitamin D deficiency has been associated with impaired resistance to infection, which may be mediated by alterations in cytokine responses. We investigated the effect of vitamin D supplementation to infants on whole blood in-vitro cytokine production and on the inflammatory marker, plasma C-reactive protein (CRP). SUBJECTS/METHODS: Blood samples were taken at 6 months of age from infants participating in the DIVIDS (Delhi Infant Vitamin D Supplementation) randomized controlled trial of weekly vitamin D supplements (1400 IU = recommended intake) from birth to 6 months with the aim of decreasing mortality and severe morbidity. We measured plasma CRP and whole blood in-vitro production of tumour necrosis factor-α (TNFα), interferon-γ (INFγ), interleukin (IL)-10 and IL-13 following no stimulation or stimulation with lipopolysaccharide or phytohemagglutinin. RESULTS: Although the intervention improved vitamin D status in a severely deficient population, there were no differences between treatment groups in plasma CRP or in the production of any of the cytokines in either unstimulated or stimulated cultures. Recent illness had limited association with immunological markers. Plasma 25-hydroxyvitamin D levels were not associated with CRP or production of any cytokines. CONCLUSIONS: Vitamin D supplementation did not affect plasma CRP or whole blood cytokine production of vitamin D-deficient low birth weight infants. This is consistent with the lack of effect of vitamin D on mortality and severe morbidity among infants in the DIVIDS trial