Can we prevent childhood asthma before birth? Summary of the VDAART results so far

Weiss, Scott T.; Litonjua, Augusto A.

doi:10.1080/17476348.2016.1227257

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…VDAART is a clinical trial to examine the hypothesis that vitamin D supplementation in pregnant women will prevent the development of asthma and allergies in their children [ 17 , 18 ]. Pregnant women between 18 and 40 years of age and at an estimated gestational age between 10 and 18 weeks were recruited at three clinical centers: Boston Medical Center, Washington University at Saint Louis, and Kaiser Permanente Southern California Region.…”

Section: Methodsmentioning

confidence: 99%

Benchmarking omics-based prediction of asthma development in children

Wang

Schaub

et al. 2023

Respir Res

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Background Asthma is a heterogeneous disease with high morbidity. Advancement in high-throughput multi-omics approaches has enabled the collection of molecular assessments at different layers, providing a complementary perspective of complex diseases. Numerous computational methods have been developed for the omics-based patient classification or disease outcome prediction. Yet, a systematic benchmarking of those methods using various combinations of omics data for the prediction of asthma development is still lacking. Objective We aimed to investigate the computational methods in disease status prediction using multi-omics data. Method We systematically benchmarked 18 computational methods using all the 63 combinations of six omics data (GWAS, miRNA, mRNA, microbiome, metabolome, DNA methylation) collected in The Vitamin D Antenatal Asthma Reduction Trial (VDAART) cohort. We evaluated each method using standard performance metrics for each of the 63 omics combinations. Results Our results indicate that overall Logistic Regression, Multi-Layer Perceptron, and MOGONET display superior performance, and the combination of transcriptional, genomic and microbiome data achieves the best prediction. Moreover, we find that including the clinical data can further improve the prediction performance for some but not all the omics combinations. Conclusions Specific omics combinations can reach the optimal prediction of asthma development in children. And certain computational methods showed superior performance than other methods.

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Section: Methodsmentioning

confidence: 99%

Benchmarking omics-based prediction of asthma development in children

Wang

Schaub

et al. 2023

Respir Res

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“…Lower rates of wheezing and asthma have been reported in the offspring of pregnant women with higher vitamin D (VD) intake, underscoring the significance of adequate perinatal VD concentrations for the developing lung (1)(2)(3)(4)(5). Accompanying the increase in asthma rates in recent decades, the prevalence of VD insufficiency in women of child-bearing age has also increased (6,7).…”

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confidence: 99%

“…Moreover, children with asthma have lower VD concentrations compared with healthy control subjects (8,9). Therefore, it is not surprising that there is a strong interest in understanding VD's role in the lungs' structural and functional development and how it may relate to asthma pathogenesis (5,10,11,12).…”

mentioning

confidence: 99%

Effect of Perinatal Vitamin D Deficiency on Lung Mesenchymal Stem Cell Differentiation and Injury Repair Potential

Sakurai

Singh

Wang

et al. 2021

Am J Respir Cell Mol Biol

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Stem cells, including the resident lung mesenchymal stem cells (LMSCs), are critically important for injury repair. Compelling evidence links perinatal vitamin D (VD) deficiency to reactive airway disease; however, the effects of perinatal VD deficiency on LMSC function is unknown. We tested the hypothesis that perinatal VD deficiency alters LMSC proliferation, differentiation, and function, leading to an enhanced myogenic phenotype. We also determined whether LMSCs' effects on alveolar type II (ATII) cell function are paracrine. Using an established rat model of perinatal VD deficiency, we studied the effects of four dietary regimens (0, 250, 500, or 1,000 IU/kg cholecalciferol-supplemented groups). At Postnatal Day 21, LMSCs were isolated, and cell proliferation and differentiation (under basal and adipogenic induction conditions) were determined. LMSC paracrine effects on ATII cell proliferation and differentiation were determined by culturing ATII cells in LMSC-conditioned media from different experimental groups.Using flow cytometry, .95% of cells were CD45-ve, .90% were CD90 1 ve, .58% were CD105 1 ve, and .64% were Stro-1 1 ve, indicating their stem cell phenotype. Compared with the VD-supplemented groups, LMSCs from the VD-deficient group demonstrated suppressed PPARc, but enhanced Wnt signaling, under basal and adipogenic induction conditions. LMSCs from 250 VD-and 500 VD-supplemented groups effectively blocked the effects of perinatal VD deficiency. LMSC-conditioned media from the VD-deficient group inhibited ATII cell proliferation and differentiation compared with those from the 250 VDand 500 VD-supplemented groups. These data support the concept that perinatal VD deficiency alters LMSC proliferation and differentiation, potentially contributing to increased respiratory morbidity seen in children born to mothers with VD deficiency.

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