Background-The gut microbiome in infancy influences immune system maturation, and may have an important impact allergic disease risk.

Background-The rise in asthma prevalence over the last few decades may be due changes in pre-natal or early life environment including maternal diet during pregnancy. Previous studies have found associations between individual foods or nutrients consumed during pregnancy and asthma or wheeze in children, but these may be confounded by overall dietary pattern.

There is intense interest in the role of vitamin D in the development of asthma and allergies. However, studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies. To address this uncertainty, the Vitamin D Antenatal Asthma Reduction Trial (VDAART) was developed. VDAART is a randomized, double-blind, placebo-controlled trial of vitamin D supplementation in pregnant women to determine whether prenatal supplementation can prevent the development of asthma and allergies in the women’s offspring. A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications, such as preeclampsia, preterm birth, and gestational diabetes. Women were randomized to the treatment arm of 4,000 IU/day of vitamin D3 plus a daily multivitamin that contained 400 IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400 IU daily of vitamin D3. Women who were between the gestational ages of 10–18 weeks were randomized from three clinical centers across the United States – Boston Medical Center, Washington University in St. Louis, and Kaiser Permanente Southern California Region (San Diego, CA). Supplementation took place throughout pregnancy. Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events. Offspring are being evaluated quarterly through questionnaires and yearly during in-person visits until the 3rd birthday of the child. Ancillary studies will investigate neonatal T-regulatory cell function, maternal vaginal flora, and maternal and child intestinal flora.

The effects of vitamin D on bone metabolism and calcium homeostasis have long been recognized. Emerging evidence has implicated vitamin D as a critical regulator of immunity, playing a role in both the innate and cell-mediated immune systems. Vitamin D deficiency has been found to be associated with several immune-mediated diseases, susceptibility to infection and cancer. Recently, there has been increasing interest in the possible link between vitamin D and asthma. Further elucidation of the role of vitamin D in lung development and immune system function may hold profound implications for the prevention and treatment of asthma. Keywords asthma; autoimmune disease; immune system regulation; T-regulatory cell; vitamin D; vitamin D deficiencyThe role of vitamin D in the regulation of calcium and bone metabolism is well established. Recently, newer physiologic functions for vitamin D have been identified. Epidemiologic and genetic studies as well as research using animal models suggest vitamin D plays a vital and complex role in immune system function and regulation. Vitamin D insufficiency has been linked with susceptibility to infection, particularly respiratory infections [1][2][3][4][5], as well as to the development of a variety of cancers [6][7][8][9][10][11] and autoimmune diseases [12][13][14][15][16] NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAsthma is one of the most common chronic diseases worldwide and has been increasing in prevalence over the last few decades [17,18]. Its exact cause remains unknown and likely has its origins in complex interactions among multiple genetic and environmental factors. Vitamin D physiologyVitamin D is an essential nutrient that humans obtain primarily through exposure to sunlight, and secondarily through diet and dietary supplements. Solar ultraviolet (UV) B (UVB) radiation converts 7-dehydrocholesterol in the skin to previtamin D 3 and subsequently to vitamin D 3 . The ability to form this prohormone is influenced by skin pigmentation, sun protection, latitude, age, amount of UV radiation exposure and coverage by clothing, any of which may significantly affect vitamin D levels. In the diet, vitamin D is found mostly in oily fish (e.g., salmon and mackerel), and in fortified grain and dairy products. Vitamin D inhibits the function of T lymphocytes both directly and via effects on antigenpresenting cells (APCs). It has potent antiproliferative effects on CD4 + T cells [49]. Essentially all published studies using both human and murine models report inhibition of Th1-associated cytokine production [46,[49][50][51][52]. More recently, vitamin D has been reported to inhibit IL-17 production [53,54]. IL-17 is an inflammatory cytokine important for defense against extracellular bacteria, but is also involved in autoimmune and allergic diseases, including asthma [55].The effects of vitamin D on Th2 responses are more complex. Most reviews simply state that vitamin D promotes Th2 responses; however, a closer look at the literature reveals...

Vitamin D deficiency was associated with lower lung function and more rapid lung function decline in smokers over 20 years in this longitudinal cohort of elderly men. This suggests that vitamin D sufficiency may have a protective effect against the damaging effects of smoking on lung function. Future studies should seek to confirm this finding in the context of smoking and other exposures that affect lung function.

ClinicalTrials.gov: NCT00920621.

Purpose of review The objective of this review is to provide an overview and discussion of recent epidemiologic and mechanistic studies of stress in relation to asthma incidence and morbidity. Recent findings Recent findings suggest that stress, whether at the individual- (i.e., epigenetics, perceived stress), family- (i.e., prenatal maternal stress, early life exposure or intimate partner violence) or community- (i.e.., neighborhood violence; neighborhood disadvantage) level influences asthma and asthma morbidity. Key recent findings regarding how psychosocial stress may influence asthma through Post Traumatic Stress Disorder (PTSD), pre-and post-natal maternal/caregiver stress, and community violence and deprivation are highlighted. Summary New research illustrates the need to further examine, characterize and address the influence of social and environmental factors (i.e., psychological stress) on asthma. Further research and innovative methodologies are needed to characterize the relationship and pathways associated with stress at multiple levels to more fully understand and address asthma morbidity, and to design potential interventions, especially to address persistent disparities in asthma in ethnic minorities and economically disadvantaged communities.

Background-Little is known about paternal psychosocial factors and childhood asthma.