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

Peer reviewe

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