Kathleen Lee-Sarwar

Association between prehospital vitamin D status and incident acute respiratory failure in critically ill patients: a retrospective cohort study

Objective We hypothesise that low 25-hydroxyvitamin D (25(OH)D) levels before hospitalisation are associated with increased risk of acute respiratory failure. Design Retrospective cohort study. Setting Medical and Surgical Intensive care units of two Boston teaching hospitals. Patients 1985 critically ill adults admitted between 1998 and 2011. Interventions None. Measurements and main results The exposure of interest was prehospital serum 25(OH)D categorised as ≤10 ng/mL, 11–19.9 ng/mL, 20–29.9 ng/mL and ≥30 ng/mL. The primary outcome was acute respiratory failure excluding congestive heart failure determined by International Classification of Diseases Ninth Edition (ICD-9) coding and validated against the Berlin Definition of acute respiratory sistress syndrome. Association between 25(OH)D and acute respiratory failure was assessed using logistic regression, while adjusting for age, race, sex, Deyo-Charlson Index and patient type (medical vs surgical). In the cohort, the mean age was 63 years, 45% were male and 80% were white; 25(OH)D was ≤10 ng/mL in 8% of patients, 11–19.9 ng/mL in 24%, 20–29.9 ng/mL in 24% and ≥30 ng/mL in 44% of patients. Eighteen per cent (n=351) were diagnosed with acute respiratory failure. Compared to patients with 25(OH)D ≥30 ng/mL, patients with lower 25(OH)D levels had significantly higher adjusted odds of acute respiratory failure (≤10 ng/mL, OR=1.84 (95% CI 1.22 to 2.77); 11–19.9 ng/mL, OR=1.60 (95% CI 1.19 to 2.15); 20–29.9 ng/mL, OR=1.37 (95% CI 1.01 to 1.86)). Conclusions Prehospital 25(OH)D was associated with the risk of acute respiratory failure in our critically ill patient cohort.

A prospective microbiome-wide association study of food sensitization and food allergy in early childhood

Alterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development.

As You Eat It: Effects of Prenatal Nutrition on Asthma

Asthma most frequently develops early in life, and increased recognition of the role of lifestyle and environmental factors in asthma susceptibility raises the possibility that dietary exposures during pregnancy may influence the risk of asthma in offspring. This review discusses the latest evidence with regard to the effect of diet during pregnancy on childhood asthma risk, including potential mechanisms, outcomes of randomized clinical trials, and results from observational studies. Vitamin D and polyunsaturated fatty acid intake during pregnancy are highlighted as areas with large and growing bodies of literature to support a potential role in prenatal modulation of subsequent asthma risk. Several other nutritional interventions are under active investigation, and recommendations regarding dietary modifications during pregnancy will likely need to be personalized based on factors such as maternal smoking and genetic variants. Although nutrition during pregnancy is uniquely challenging to investigate, and definitive recommendations cannot be made without additional high-quality evidence and knowledge regarding long-term effects of interventions, the modifiable nature of the diet and sizeable potential reduction of morbidity supports ongoing research to determine how to optimize nutrition during pregnancy to prevent asthma in offspring.

Prenatal and early-life triclosan and paraben exposure and allergic outcomes

Background: In cross‐sectional studies triclosan and parabens, ubiquitous ingredients in personal care and other products, are associated with allergic disease. Objectives: We investigated the association between prenatal and early‐life triclosan and paraben exposure and childhood allergic disease in a prospective longitudinal study. Methods: Subjects were enrollees in the Vitamin D Antenatal Asthma Reduction Trial. Triclosan, methyl paraben, and propyl paraben concentrations were quantified in maternal plasma samples pooled from the first and third trimesters and urine samples from children at age 3 or 4 years. Outcomes were parental report of physician‐diagnosed asthma or recurrent wheezing and allergic sensitization to food or environmental antigens based on serum specific IgE levels at age 3 years in high‐risk children. Results: The analysis included 467 mother‐child pairs. Overall, there were no statistically significant associations of maternal plasma or child urine triclosan or paraben concentrations with asthma or recurrent wheeze or food or environmental sensitization at age 3 years. A trend toward an inverse association between triclosan and paraben exposure and allergic sensitization was observed. There was evidence of effect measure modification by sex, with higher odds of environmental sensitization associated with increasing paraben concentrations in male compared with female subjects. Conclusions: We did not identify a consistent association between prenatal and early‐life triclosan or paraben concentrations and childhood asthma, recurrent wheeze, or allergic sensitization in the overall study population. The differential effects of triclosan or paraben exposure on allergic sensitization by sex observed in this study warrant further exploration.

Intestinal microbial-derived sphingolipids are inversely associated with childhood food allergy

Intestinal Bacteroides-derived sphingolipids in infancy were inversely associated with food allergy among sensitized subjects. This may be mediated in part by invariant NK T cell activation.

Strategies to alter the natural history of childhood asthma

Purpose of reviewAsthma exhibits significant heterogeneity in occurrence and severity over the lifespan. Our goal is to discuss recent evidence regarding determinants of the natural history of asthma during childhood, and review the rationale behind and status of major efforts to alter its course. Recent findingsVariations in microbial exposures are associated with risk of allergic disease, and the use of bacterial lysates may be a promising preventive strategy. Exposure to air pollution appears to be particularly damaging in prenatal and early life, and interventions to reduce pollution are feasible and result in clinical benefit. E-cigarette use may have a role in harm reduction for conventional cigarette smokers with asthma, but has undefined short-term and long-term effects that must be clarified. Vitamin D insufficiency over the first several years of life is associated with risk of asthma, and vitamin D supplementation reduces the risk of severe exacerbations. SummaryThe identification of risk factors for asthma occurrence, persistence and severity will continue to guide efforts to alter the natural history of the disease. We have reviewed several promising strategies that are currently under investigation. Vitamin D supplementation and air pollution reduction have been shown to be effective strategies and warrant increased investigation and implementation.

Effects of exclusive breastfeeding on infant gut microbiota: a meta-analysis across studies and populations

Literature regarding the differences in gut microbiota between exclusively breastfed (EBF) and non-EBF infants is meager with large variation in methods and results. We performed a meta-analysis of seven studies (a total of 1825 stool samples from 684 infants) to investigate effects of EBF compared to non-EBF on infant gut microbiota across different populations. In the first 6 months of life, overall bacterial diversity, gut microbiota age, relative abundances of Bacteroidetes and Firmicutes and microbial-predicted pathways related to carbohydrate metabolism were consistently increased; while relative abundances of pathways related to lipid, vitamin metabolism and detoxification were decreased in non-EBF vs. EBF infants. The perturbation in microbial-predicted pathways associated with non-EBF was larger in infants delivered by C-section than delivered vaginally. Longer duration of EBF mitigated diarrhea-associated gut microbiota dysbiosis and the effects of EBF persisted after 6 months of age. These consistent findings across vastly different populations suggest that one of the mechanisms of short and long-term benefits of EBF may be alteration in gut microbes.

Diet during Pregnancy and Infancy and the Infant Intestinal Microbiome

Objectives To determine the association between diet during pregnancy and infancy, including breastfeeding vs formula feeding, solid food introduction, and the infant intestinal microbiome. Study design Infants participating in the Vitamin D Antenatal Asthma Reduction Trial were included in this study (n = 323). Maternal and infant diets were assessed by questionnaire. Infant stool samples were collected at age 3‐6 months. Stool sequencing was performed using the Roche 454 platform. Analyses were stratified by race/ethnicity. Results Breastfeeding, compared with formula feeding, was independently associated with infant intestinal microbial diversity. Breastfeeding also had the most consistent associations with individual taxa that have been previously linked to early‐life diet and health outcomes (eg, Bifidobacterium). Maternal diet during pregnancy and solid food introduction were less associated with the infant gut microbiome than breastfeeding status. We found evidence of a possible interaction between breastfeeding and child race/ethnicity on microbial composition. Conclusions Breastfeeding vs formula feeding is the dietary factor that is most consistently independently associated with the infant intestinal microbiome. The relationship between breastfeeding status and intestinal microbiome composition varies by child race/ethnicity. Future studies will need to investigate factors, including genomic factors, which may influence the response of the microbiome to diet. Trial registration ClinicalTrials.gov: NCT00920621.

Dietary and plasma polyunsaturated fatty acids are inversely associated with asthma and atopy in early childhood

BACKGROUND Polyunsaturated fatty acids (PUFAs) influence immune function and risk of allergic disease. Prior evidence of the effect of PUFA intake on childhood asthma and allergy is inconclusive. OBJECTIVES To investigate associations of PUFA plasma levels and dietary intake with asthma and allergy at age 3 years in this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial. METHODS Plasma PUFA levels were reported as relative abundances from mass spectrometry profiling, and dietary PUFA intake was derived from food frequency questionnaire responses. Associations between PUFA and outcomes, including asthma and/or recurrent wheeze, allergic sensitization, and total IgE at age 3 years, were evaluated in adjusted regression models. Additional regression models analyzed the combined effects of antenatal vitamin D and early childhood PUFA on outcomes. RESULTS Total, omega-3, and omega-6 plasma PUFA relative abundances were significantly (P < .05) inversely associated with both asthma and/or recurrent wheeze and allergic sensitization. Likewise, dietary PUFA intake was inversely associated with asthma and/or recurrent wheeze (P < .05 for omega-6 PUFA only). For both dietary and plasma measures of total, omega-3, and omega-6 PUFAs, inverse associations with outcomes were strongest among subjects with both high umbilical cord blood 25-hydroxyvitamin D and high PUFA at age 3 years. CONCLUSIONS PUFA dietary intake and plasma levels are inversely associated with asthma and/or recurrent wheeze and atopy at age 3 years. Antenatal vitamin D could modulate the effect of early childhood PUFA on risk of asthma and allergy.

Partial Least Squares Discriminant Analysis and Bayesian Networks for Metabolomic Prediction of Childhood Asthma

To explore novel methods for the analysis of metabolomics data, we compared the ability of Partial Least Squares Discriminant Analysis (PLS-DA) and Bayesian networks (BN) to build predictive plasma metabolite models of age three asthma status in 411 three year olds (n = 59 cases and 352 controls) from the Vitamin D Antenatal Asthma Reduction Trial (VDAART) study. The standard PLS-DA approach had impressive accuracy for the prediction of age three asthma with an Area Under the Curve Convex Hull (AUCCH) of 81%. However, a permutation test indicated the possibility of overfitting. In contrast, a predictive Bayesian network including 42 metabolites had a significantly higher AUCCH of 92.1% (p for difference < 0.001), with no evidence that this accuracy was due to overfitting. Both models provided biologically informative insights into asthma; in particular, a role for dysregulated arginine metabolism and several exogenous metabolites that deserve further investigation as potential causative agents. As the BN model outperformed the PLS-DA model in both accuracy and decreased risk of overfitting, it may therefore represent a viable alternative to typical analytical approaches for the investigation of metabolomics data.