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The use of electronic cigarettes is growing, and some hope that they will replace what is felt to be the more dangerous nicotine-delivery system — cigarettes. However, data on the long-term safety of e-cigarettes are still being gathered. Electronic cigarettes (e-cigarettes), also known as electronic nicotine-delivery systems, are devices that produce an aerosol by heating a liquid that contains a solvent (vegetable glycerin, propylene glycol, or a mixture of these), one or more flavorings, and nicotine, although the nicotine may be omitted. The evaporation of the liquid at the heating element is followed by rapid cooling to form an aerosol. This process is fundamentally different from the combustion of tobacco, and consequently the composition of the aerosol from e-cigarettes and the smoke from tobacco is quite different. E-cigarette aerosol is directly inhaled (or “vaped”) by the user through . . .

In a previously published controlled trial, maternal administration of vitamin D during pregnancy was found to protect against wheeze in the offspring at the age of 3 years. In this follow-up study involving the same children at the age of 6 years, that supplementation no longer had a protective effect.

The prevalence of tobacco smoking in the United States has declined to 14.0% but still exceeds 25% among high-risk subgroups. 1,2 Electronic cigarettes (e-cigarettes) are not approved by the Food and Drug Administration (FDA) for smoking cessation, but Americans trying to quit smoking use these products more frequently than FDA-approved cessation aids. 3 Comparative-effectiveness trials are needed to learn whether smokers have a better chance of quitting with e-cigarettes. Previous trials have had methodologic shortcomings, used first-generation e-cigarettes, or did not assess long-term outcomes. Hajek et al. 4 now report in the Journal the results of a multicenter, pragmatic, randomized trial of e-cigarettes, . . .

The relationship between the development and/or progression of interstitial lung abnormalities (ILA) and clinical outcomes has not been previously investigated. To determine the risk factors for, and the clinical consequences of, having ILA progression in participants from the Framingham Heart Study. ILA were assessed in 1,867 participants who had serial chest computed tomography (CT) scans approximately 6 years apart. Mixed effect regression (and Cox) models were used to assess the association between ILA progression and pulmonary function decline (and mortality). During the follow-up period 660 (35%) participants did not have ILA on either CT scan, 37 (2%) had stable to improving ILA, and 118 (6%) had ILA with progression (the remaining participants without ILA were noted to be indeterminate on at least one CT scan). Increasing age and increasing copies of the MUC5B promoter polymorphism were associated with ILA progression. After adjustment for covariates, ILA progression was associated with a greater FVC decline when compared with participants without ILA (20 ml; SE, ±6 ml; P = 0.0005) and with those with ILA without progression (25 ml; SE, ±11 ml; P = 0.03). Over a median follow-up time of approximately 4 years, after adjustment, ILA progression was associated with an increase in the risk of death (hazard ratio, 3.9; 95% confidence interval, 1.3-10.9; P = 0.01) when compared with those without ILA. These findings demonstrate that ILA progression in the Framingham Heart Study is associated with an increased rate of pulmonary function decline and increased risk of death.

Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults. To determine if exposure to traffic and PM2.5 is associated with longitudinal changes in lung function in a population-based cohort in the Northeastern United States, where pollution levels are relatively low. FEV1 and FVC were measured up to two times between 1995 and 2011 among 6,339 participants of the Framingham Offspring or Third Generation studies. We tested associations between residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by a land-use model using satellite measurements of aerosol optical thickness) and lung function. We examined differences in average lung function using mixed-effects models and differences in lung function decline using linear regression models. Current smokers were excluded. Models were adjusted for age, sex, height, weight, pack-years, socioeconomic status indicators, cohort, time, season, and weather. Living less than 100 m from a major roadway was associated with a 23.2 ml (95% confidence interval [CI], -44.4 to -1.9) lower FEV1 and a 5.0 ml/yr (95% CI, -9.0 to -0.9) faster decline in FEV1 compared with more than 400 m. Each 2 μg/m(3) increase in average of PM2.5 was associated with a 13.5 ml (95% CI, -26.6 to -0.3) lower FEV1 and a 2.1 ml/yr (95% CI, -4.1 to -0.2) faster decline in FEV1. There were similar associations with FVC. Associations with FEV1/FVC ratio were weak or absent. Long-term exposure to traffic and PM2.5, at relatively low levels, was associated with lower FEV1 and FVC and an accelerated rate of lung function decline.

Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations. Respiratory infections are the principal cause of asthma exacerbations in children. Altman and colleagues use a systems approach to describe the pathways associated with asthma exacerbations in a cohort of inner-city children.

Background As omics measurements profiled on different molecular layers are interconnected, integrative approaches that incorporate the regulatory effect from multi-level omics data are needed. When the multi-level omics data are from the same individuals, gene expression (GE) clusters can be identified using information from regulators like genetic variants and DNA methylation. When the multi-level omics data are from different individuals, the choice of integration approaches is limited. Methods We developed an approach to improve GE clustering from microarray data by integrating regulatory data from different but partially overlapping sets of individuals. We achieve this through (1) decomposing gene expression into the regulated component and the other component that is not regulated by measured factors, (2) optimizing the clustering goodness-of-fit objective function. We do not require the availability of different omics measurements on all individuals. A certain amount of individual overlap between GE data and the regulatory data is adequate for modeling the regulation, thus improving GE clustering. Results A simulation study shows that the performance of the proposed approach depends on the strength of the GE-regulator relationship, degree of missingness, data dimensionality, sample size, and the number of clusters. Across the various simulation settings, the proposed method shows competitive performance in terms of accuracy compared to the alternative K-means clustering method, especially when the clustering structure is due mostly to the regulated component, rather than the unregulated component. We further validate the approach with an application to 8,902 Framingham Heart Study participants with data on up to 17,873 genes and regulation information of DNA methylation and genotype from different but partially overlapping sets of participants. We identify clustering structures of genes associated with pulmonary function while incorporating the predicted regulation effect from the measured regulators. We further investigate the over-representation of these GE clusters in pathways of other diseases that may be related to lung function and respiratory health. Conclusion We propose a novel approach for clustering GE with the assistance of regulatory data that allowed for different but partially overlapping sets of individuals to be included in different omics data.

Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards. To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study. We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995-2011) who were not current smokers, with previous-day pollutant levels in compliance with EPA standards. We compared lung function (FEV1 and FVC) after previous-day exposure to particulate matter less than 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in the \"moderate\" range of the EPA Air Quality Index to exposure in the \"good\" range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function. Exposure to pollutant concentrations in the \"moderate\" range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV1 for PM2.5 (95% confidence interval [CI], -33.4, -6.9), a 30.6-ml lower FEV1 for NO2 (95% CI, -60.9, -0.2), and a 55.7-ml lower FEV1 for O3 (95% CI, -100.7, -10.8) compared with the \"good\" range. The 1- and 2-day moving averages of PM2.5, NO2, and O3 before testing were negatively associated with FEV1 and FVC. Short-term exposure to PM2.5, NO2, and O3 within current EPA standards was associated with lower lung function in this cohort of adults.

Variants in the gene encoding mucin 5B ( MUC5B ) have been associated with interstitial fibrosis. This study shows a relationship between the presence of the associated variants in MUC5B and interstitial lung abnormalities in participants in a Framingham study cohort. Subclinical interstitial lung abnormalities are relatively common findings on imaging studies in smokers and elderly persons. 1 Accumulating evidence suggests that these abnormalities may precede the development of clinically relevant pulmonary fibrosis. 1 – 7 However, it is not known whether there is a genetic association between interstitial lung abnormalities and pulmonary fibrosis in the general population. Recently, a single-nucleotide polymorphism (SNP) (rs35705950) in the promoter of the gene encoding mucin 5B ( MUC5B ) was shown to be associated with both familial interstitial pneumonia and sporadic idiopathic pulmonary fibrosis. 8 In addition, the MUC5B variant was associated with increased expression of MUC5B in . . .

BackgroundThe gut microbiota has been associated with overweight and obesity in adults, but the evidence in children is limited. Our aim was to study whether composition of the gut microbiota at the age of 3 years is associated with overweight/obesity in children cross-sectionally.MethodsChildren, who participated in a clinical trial of prenatal vitamin-D supplementation (VDAART), underwent standardized height and weight measurements, and collection of stool samples at 3 years of age. 16 S rRNA sequencing (V4 region) of the stool samples were performed with Illumina MiSeq. Associations between microbiota and overweight/obesity (body mass index z-scores >85th percentile) was analyzed using logistic regression.ResultsOut of 502 children, 146 (29%) were categorized as overweight/obese. Maternal pre-pregnancy BMI, birth weight and length, formula feeding during the first year, high frequency of fast food consumption, and time watching TV or computer screen at 3 years were the risk factors for overweight/obesity. Of the top 20 most abundant genera, high relative abundance of Parabacteroidetes (Bacteroidetes; Bacteroidales) (aOR(95% CI): 0.69 (0.53, 0.90, p = 0.007) per interquartile increase) and unassigned genus within Peptostreptococcae family were inversely associated with overweight/obesity, whereas high relative abundance of Dorea (Firmicutes;Clostridiales) (1.23 (1.05, 1.43, p = 0.009)) was positively associated. Associations were independent of each other. No associations were found between diversity indices and overweight/obesity.ConclusionsOur data suggest that some of the differences in gut composition of bacteria between obese and non-obese adults can already be observed in 3-year old children. Longitudinal studies will be needed to determine long-term effects.