Rationale: Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood. Objectives: To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood. Methods: We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses. Measurements and Main Results: Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (,30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log 10 unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.71; P 5 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05-0.67; P 5 0.01), and increased airway responsiveness (a <8.58-mmol provocative dose of methacholine producing a 20% fall in baseline FEV 1 [OR, 0.15; 95% CI, 0.024-0.97; P 5 0.05]). Conclusions: Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity.For unclear reasons, the prevalence of allergic diseases and asthma increased from a period likely preceding the 1960s to the 1990s (1). Worldwide surveys have shown that asthma prevalence is highest in industrialized nations (2). Although there is a trend for increased prevalence of asthma in countries farthest from the equator, some nations near the equator have high asthma prevalence (e.g., Costa Rica) (2).Results of some, but not all, epidemiologic studies suggest that vitamin D deficiency is associated with an increased incidence of asthma symptoms (3-5). Our group has shown that higher maternal intakes of vitamin D during pregnancy are associated with decreased risks for recurrent wheeze in young children (6, 7), suggesting that vitamin D may play a role in the development of asthma. However, among those with established asthma, vitamin D may have a role in the manifestation of the disorder. Findings from in vitro studies (8) suggest that vitamin D may reverse steroid resistance in individuals with asthma, thus suggesting that vitamin D may play a role in the control of asthma. However, there has been no epidemiologic study of the relation between serum vitamin D levels and markers of asthma severity. The aim of the current analysis, therefore, was to examine the relationship ...

Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk, and obese asthmatic patients have more symptoms, more frequent and severe exacerbations, reduced response to several asthma medications, and decreased quality of life. Obese asthma is a complex syndrome, including different phenotypes of disease that are just beginning to be understood. We examine the epidemiology and characteristics of this syndrome in children and adults, as well as the changes in lung function seen in each age group. We then discuss the better recognized factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, and the genetics/genomics of obese asthma. Finally, we describe current evidence on the effect of weight loss and mention some important future directions for research in the field.

In order to summarize the principal findings on risk and protective factors for childhood asthma, we retrieved systematic reviews on these topics in children (ages 1 to 18 years), up to January 2016, through MEDLINE, EMBASE, CINAHL, SCOPUS and CDSR. Two hundred twenty seven studies were searched from databases. Among those, 41 systematic reviews (SRs) were included: 9 focused on prenatal factors, 5 on perinatal factors, and 27 on postnatal factors. Of these 41 SRs, 83% had good methodological quality, as determined by the AMSTAR tool. After reviewing all evidence, parental asthma, prenatal environmental tobacco smoke and prematurity (particularly very preterm birth) are well-established risk factors for childhood asthma. Current findings do suggest mild to moderate causal effects of certain modifiable behaviors or exposures during pregnancy (maternal weight gain or obesity, maternal use of antibiotics or paracetamol, and maternal stress), the perinatal period (birth by Caesarean delivery), or postnatal life (severe RSV infection, overweight or obesity, indoor exposure to mold or fungi, and outdoor air pollution) on childhood asthma, but this suggestive evidence must be confirmed in interventional studies or (if interventions are not feasible) well-designed prospective studies.

Rationale: Vitamin D insufficiency (a serum 25(OH)D ,30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. Objectives: To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. Methods: A cross-sectional study was conducted of 560 children ages 6-14 years with (n ¼ 287) and without (n ¼ 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genomewide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Measurements and Main Results: Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P ¼ 0.001) and atopy, and a lower FEV 1 /FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2-21.6; P ¼ 0.002) than in atopic (OR, 2; 95% CI, 1-4.1; P ¼ 0.04) cases. Conclusions: Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.Keywords: vitamin D; asthma exacerbations; Puerto Ricans; childhood Vitamin D insufficiency (a serum level of 25(OH)D ,30 ng/ml) is common among children in the United States mainland. For example, a nationwide study of 2,759 U.S. children ages 6-11 years found vitamin D insufficiency in approximately 62% of nonHispanic whites, approximately 86% of Hispanics, and approximately 96% of non-Hispanic blacks (1). Vitamin D insufficiency has been associated with increased asthma morbidity, particularly severe disease exacerbations, in observational studies of children of school age in Costa Rica (2) and North America (3).Although current evidence from observational (2-5) and experimental studies (6-9) suggests that vitamin D insufficiency leads to severe asthma exacerbations or increased asthma morbidity in childhood (10), no study of vitamin D and asthma morbidity has accounted for objectively assessed racial ancestry and time spent outdoors. This is critical to exclude whether vitamin D insufficiency is associated with severe asthma exacerbations or asthma morbidity through "reverse causation" (e.g., more severe asthma leading to reduced time outdoors and thus decreased exposure to sunlight ...

WHAT'S KNOWN ON THIS SUBJECT:The intestinal microbiome may play a role in immune system maturation, and it has been postulated that early-life probiotic administration may reduce the risk of allergies and asthma in childhood. To date, however, results from clinical trials have been inconsistent. WHAT THIS STUDY ADDS:In this meta-analysis, administration of probiotics in early life may reduce total immunoglobulin E level and protect against atopic sensitization but do not seem to protect against asthma/wheezing. Future trials should carefully select probiotic strains and include longer follow-up. abstract BACKGROUND AND OBJECTIVE: Probiotics may reduce the risk of atopy and asthma in children. However, results from clinical trials have been conflicting, and several of them may have been underpowered. We performed a meta-analysis of randomized, placebo-controlled trials to assess the effects of probiotic supplementation on atopic sensitization and asthma/wheeze prevention in children. METHODS:Random-effects models were used to calculate pooled risk estimates. Meta-regression was conducted to examine the effect of potential factors on probiotics efficacy.RESULTS: Probiotics were effective in reducing total immunoglobulin E (IgE) (mean reduction: -7.59 U/mL [95% confidence interval (CI): -14.96 to -0.22]; P = .044). Meta-regression showed that the reduction in IgE was more pronounced with longer follow-up. Probiotics significantly reduced the risk of atopic sensitization when administered prenatally (relative risk: 0.88 [95% CI: 0.78 to 0.99]; P = .035 for positive result on the skin prick test and/or elevated specific IgE to common allergens) and postnatally (relative risk: 0.86 [95% CI: 0.75 to 0.98]; P = .027 for positive result on skin prick test). Administration of Lactobacillus acidophilus, compared with other strains, was associated with an increased risk of atopic sensitization (P = .002). Probiotics did not significantly reduce asthma/wheeze (relative risk: 0.96 [95% CI: 0.85 to 1.07]).CONCLUSIONS: Prenatal and/or early-life probiotic administration reduces the risk of atopic sensitization and decreases the total IgE level in children but may not reduce the risk of asthma/wheeze. Follow-up duration and strain significantly modified these effects. Future trials for asthma prevention should carefully select probiotic strain and consider longer follow-up. Pediatrics 2013;132:e666-e676 AUTHORS:

Background The mechanisms and consequences of the observed association between obesity and childhood asthma are unclear. Objectives To determine the effect of obesity on treatment responses to inhaled corticosteroids in asthmatic children. Methods We performed a post hoc analysis to evaluate the interaction between body mass index (BMI) and treatment with inhaled budesonide on lung function in the Childhood Asthma Management Program (CAMP) trial. Participants were then stratified into overweight/obese and non-overweight, and their response to inhaled budesonide was analyzed longitudinally over the 4 years of the trial. Results There was a significant interaction between BMI and budesonide for pre-BD FEV1/FVC (P=0.0007) and bronchodilator response (BDR) (P=0.049), and a non-significant trend for an interaction between BMI and budesonide on pre-BD FEV1 (P=0.15). Non-overweight children showed significant improvement with inhaled budesonide in lung function (FEV1, FEV1/FVC, and BDR) during the early (years 1–2) and late stages (years 3–4) of the trial. Overweight/obese children had improved FEV1 and BDR during the early but not the late stage of the trial, and showed no improvement in FEV1/FVC. When comparing time points where both groups showed significant response, the degree of improvement among non-overweight children was significantly greater than in overweight/obese children at most visits. Non-overweight children had a 44% reduction in the risk of ER visits or hospitalizations throughout the trial (P=0.001); there was no reduction in risk among overweight/obese (P=0.97). Conclusions Compared to children of normal weight, overweight/obese children in CAMP showed a decreased response to inhaled budesonide on measures of lung function and ER visits/hospitalizations for asthma.

Obesity is detrimental to lung function, but specific patterns differ between children and adults. Physicians should be aware of adverse effects of obesity on lung function, and weight control should be considered in the management of airway disease among the obese.

Background: Epigenetic mechanisms may alter the airway epithelial barrier and ultimately lead to atopic diseases such as asthma. Here we aim to identify DNA methylation profiles that are associated with-and accurately classify-atopy and atopic asthma in school-aged children.