Vitamin D supplementation in children with asthma: a systematic review and meta-analysis.

BACKGROUND: Epidemiologic studies suggest an association between vitamin D deficiency and atopic diseases, including asthma. The objective of this study was to systematically review the benefits and harms of vitamin D supplementation in children with asthma. METHODS: We used standard Cochrane systematic review methodology. The search strategy included an electronic search in February 2013 of MEDLINE and EMBASE. Two reviewers completed in duplicate and independently study selection, data abstraction, and assessment of risk of bias. We pooled the results of trials using a random-effects model. We assessed the quality of evidence by outcome using the GRADE methodology. RESULTS: Four trials with a total of 149 children met eligibility criteria. The trials had major methodological limitations. Given the four studies reporting on asthma symptoms used different instruments to measure that outcome, we opted not to conduct a meta-analysis. Three of those studies reported improvement in asthma symptoms in the vitamin D supplemented group study, while the fourth reported no effect (very low quality evidence). For the lung function outcome, a meta-analysis of two trials assessing post treatment FEV-1 found a mean difference of 0.54 liters per second (95% CI -5.28; 4.19; low quality evidence). For the vitamin D level outcome, a meta-analysis of three trials found a mean difference of 6.56 ng/ml (95% CI -0.64; 13.77; very low quality evidence). CONCLUSIONS: The available very low to low quality evidence does not confirm or rule out beneficial effects of vitamin D supplementation in children with asthma. Large-scale, well-designed and executed randomized controlled trials are needed to better understand the effectiveness and safety of vitamin D in children with asthma.

Activated protein C attenuates acute lung injury and apoptosis in a hyperoxic animal model.

Evidence suggests that activated protein C (APC) attenuates acute lung injury (ALI) through antithrombotic and anti-inflammatory mechanisms. The aim of this study was to determine the effects of APC on ALI in adult rats exposed to hyperoxic environment. Rats were divided into control, hyperoxia, hyperoxia + APC, and APC. Hyperoxia and hyperoxia + APC were exposed to 1, 3, and 5 days of hyperoxia. Hyperoxia + APC and APC were injected with APC (5 mg/kg, i.p.) every 12 h. Control and hyperoxia received isotonic sodium chloride solution injection. Measurement of wet to dry ratio and albumin leak demonstrated significant improvement in hyperoxia + APC when compared with hyperoxia. Apoptosis, as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, was significantly reduced in hyperoxia + APC when compared with hyperoxia. Histological evaluation of lung sections showed significant reduction in inflammation, edema, and in the number of marginating neutrophils in hyperoxia + APC as compared with hyperoxia. Transcriptional expression of lung inflammatory mediators demonstrated a time-dependent surge in the levels TNF-alpha, IL-1beta, and IL-6 in response to hyperoxia that was attenuated with APC administration in the presence of hyperoxia. In this rat model, APC attenuates lung injury and the expression of inflammatory mediators in ALI secondary to hyperoxia.

Apoptosis and the activity of ceramide, Bax and Bcl-2 in the lungs of neonatal rats exposed to limited and prolonged hyperoxia.

BACKGROUND: The aim of the study is to examine the effect of limited and prolonged hyperoxia on neonatal rat lung. This is done by examining the morphologic changes of apoptosis, the expression of ceramide, an important mediator of apoptosis, the expression of inflammatory mediators represented by IL-1beta and the expression of 2 proto-oncogenes that appear to modulate apoptosis (Bax and Bcl-2). METHODS: Newborn rats were placed in chambers containing room air or oxygen above 90% for 7 days. The rats were sacrificed at 3, 7 or 14 days and their lungs removed. Sections were fixed, subjected to TUNEL, Hoechst, and E-Cadherin Staining. Sections were also incubated with anti-Bcl-2 and anti-Bax antisera. Bcl-2 and Bax were quantitated by immunohistochemistry. Lipids were extracted, and ceramide measured through a modified diacylglycerol kinase assay. RT-PCR was utilized to assess IL-1beta expression. RESULTS: TUNEL staining showed significant apoptosis in the hyperoxia-exposed lungs at 3 days only. Co-staining of the apoptotic cells with Hoechst, and E-Cadherin indicated that apoptotic cells were mainly epithelial cells. The expression of Bax and ceramide was significantly higher in the hyperoxia-exposed lungs at 3 and 14 days of age, but not at 7 days. Bcl-2 was significantly elevated in the hyperoxia-exposed lungs at 3 and 14 days. IL-1beta expression was significantly increased at 14 days. CONCLUSION: Exposure of neonatal rat lung to hyperoxia results in early apoptosis documented by TUNEL assay. The early rise in Bax and ceramide appears to overcome the anti-apoptotic activity of Bcl-2. Further exposure did not result in late apoptotic changes. This suggests that apoptotic response to hyperoxia is time sensitive. Prolonged hyperoxia results in acute lung injury and the shifting balance of ceramide, Bax and Bcl-2 may be related to the evolution of the inflammatory process.