Clinical and epidemiological data suggest that asthma and allergic diseases are associated and may share a common genetic etiology. We analyzed genome-wide SNP data for asthma and allergic diseases ...in 33,593 cases and 76,768 controls of European ancestry from UK Biobank. Two publicly available independent genome-wide association studies were used for replication. We have found a strong genome-wide genetic correlation between asthma and allergic diseases (r
= 0.75, P = 6.84 × 10
). Cross-trait analysis identified 38 genome-wide significant loci, including 7 novel shared loci. Computational analysis showed that shared genetic loci are enriched in immune/inflammatory systems and tissues with epithelium cells. Our work identifies common genetic architectures shared between asthma and allergy and will help to advance understanding of the molecular mechanisms underlying co-morbid asthma and allergic diseases.
Tumor histology is an important predictor of therapeutic response and outcomes in lung cancer. Tissue sampling for pathologist review is the most reliable method for histology classification, ...however, recent advances in deep learning for medical image analysis allude to the utility of radiologic data in further describing disease characteristics and for risk stratification. In this study, we propose a radiomics approach to predicting non-small cell lung cancer (NSCLC) tumor histology from non-invasive standard-of-care computed tomography (CT) data. We trained and validated convolutional neural networks (CNNs) on a dataset comprising 311 early-stage NSCLC patients receiving surgical treatment at Massachusetts General Hospital (MGH), with a focus on the two most common histological types: adenocarcinoma (ADC) and Squamous Cell Carcinoma (SCC). The CNNs were able to predict tumor histology with an AUC of 0.71(p = 0.018). We also found that using machine learning classifiers such as k-nearest neighbors (kNN) and support vector machine (SVM) on CNN-derived quantitative radiomics features yielded comparable discriminative performance, with AUC of up to 0.71 (p = 0.017). Our best performing CNN functioned as a robust probabilistic classifier in heterogeneous test sets, with qualitatively interpretable visual explanations to its predictions. Deep learning based radiomics can identify histological phenotypes in lung cancer. It has the potential to augment existing approaches and serve as a corrective aid for diagnosticians.
Environmental manganese exposure has been associated with adverse neurodevelopmental outcomes among school-aged children; yet, few studies have evaluated prenatal exposure.
Our study examines ...associations between prenatal manganese concentrations and placental transfer of manganese with neurodevelopment in 224 2-y-old children residing near the Tar Creek Superfund Site.
We collected maternal and cord blood at delivery, measured manganese using inductively coupled plasma mass spectrometry, and assessed neurodevelopment using the Bayley Scales of Infant Development-II. Associations between manganese and mental (MDI) and psychomotor (PDI) development indices were estimated in multivariable models. Placental transfer, approximated by cord/maternal manganese ratio, cord/total manganese ratio (total=maternal+cord), and by joint classification according to high or low (above or below median) maternal and cord manganese, was evaluated as a predictor of neurodevelopment.
Median levels interquartile ranges (IQR) of manganese in maternal and cord blood, respectively, were 24.0 (19.5-29.7) and 43.1 (33.5-52.1) μg/L. Adjusting for lead, arsenic, and other potential confounders, an IQR increase in maternal manganese was associated with -3.0 (95% CI: -5.3, -0.7) points on MDI and -2.3 (95% CI: -4.1, -0.4) points on PDI. Cord manganese concentrations were not associated with neurodevelopment scores. Cord/maternal and cord/total manganese ratios were positively associated with MDI cord/maternal: β=2.6 (95% Cl: −0.04, 5.3); cord/total: β=22.0 (95% Cl: 3.2, 40.7) and PDI (cord/maternal: β=1.7 (95% Cl: −0.5, 3.9); cord/total: β=15.6 (95% Cl: 0.3, 20.9)). Compared to mother-child pairs with low maternal and cord manganese, associations with neurodevelopment scores were negative for pairs with either high maternal, high cord, or high maternal and cord manganese.
Maternal blood manganese concentrations were negatively associated with early childhood neurodevelopment scores in our study. Findings highlight the importance of understanding maternal exposures during pregnancy and factors influencing placental transfer. https://doi.org/10.1289/EHP925.
This study aimed to investigate the quantitative effects of outdoor air pollution, represented by 10 µg/m(3) increment of PM10, on chronic obstructive pulmonary disease in China, United States and ...European Union through systematic review and meta-analysis.
Publications in English and Chinese from PubMed and EMBASE were selected. The Cochrane Review Handbook of Generic Inverse Variance was used to synthesize the pooled effects on incidence, prevalence, mortality and hospital admission.
Outdoor air pollution contributed to higher incidence and prevalence of COPD. Short-term exposure was associated with COPD mortality increased by 6%, 1% and 1% in the European Union, the United States and China, respectively (p < 0.05). Chronic PM exposure produced a 10% increase in mortality. In a short-term exposure to 10 µg/m(3) PM10 increment COPD mortality was elevated by 1% in China (p < 0.05) and hospital admission enrollment was increased by 1% in China, 2% in United States and 1% in European Union (p < 0.05).
Outdoor air pollution contributes to the increasing burdens of COPD.10 µg/m(3) increase of PM10 produced significant condition of COPD death and exacerbation in China, United States and European Union. Controlling air pollution will have substantial benefit to COPD morbidity and mortality.
Recent interest in reference-free deconvolution of DNA methylation data has led to several supervised methods, but these methods do not easily permit the interpretation of underlying cell types.
We ...propose a simple method for reference-free deconvolution that provides both proportions of putative cell types defined by their underlying methylomes, the number of these constituent cell types, as well as a method for evaluating the extent to which the underlying methylomes reflect specific types of cells. We demonstrate these methods in an analysis of 23 Infinium data sets from 13 distinct data collection efforts; these empirical evaluations show that our algorithm can reasonably estimate the number of constituent types, return cell proportion estimates that demonstrate anticipated associations with underlying phenotypic data; and methylomes that reflect the underlying biology of constituent cell types.
Our methodology permits an explicit quantitation of the mediation of phenotypic associations with DNA methylation by cell composition effects. Although more work is needed to investigate functional information related to estimated methylomes, our proposed method provides a novel and useful foundation for conducting DNA methylation studies on heterogeneous tissues lacking reference data.
The term interstitial lung abnormalities refers to specific CT findings that are potentially compatible with interstitial lung disease in patients without clinical suspicion of the disease. ...Interstitial lung abnormalities are increasingly recognised as a common feature on CT of the lung in older individuals, occurring in 4-9% of smokers and 2-7% of non-smokers. Identification of interstitial lung abnormalities will increase with implementation of lung cancer screening, along with increased use of CT for other diagnostic purposes. These abnormalities are associated with radiological progression, increased mortality, and the risk of complications from medical interventions, such as chemotherapy and surgery. Management requires distinguishing interstitial lung abnormalities that represent clinically significant interstitial lung disease from those that are subclinical. In particular, it is important to identify the subpleural fibrotic subtype, which is more likely to progress and to be associated with mortality. This multidisciplinary Position Paper by the Fleischner Society addresses important issues regarding interstitial lung abnormalities, including standardisation of the definition and terminology; predisposing risk factors; clinical outcomes; options for initial evaluation, monitoring, and management; the role of quantitative evaluation; and future research needs.
Air quality has improved and smoking rates have declined over the past half-century in the US. It is unknown whether such secular improvements, and other policies, have helped close socioeconomic ...gaps in respiratory health.
To describe long-term trends in socioeconomic disparities in respiratory disease prevalence, pulmonary symptoms, and pulmonary function.
This repeated cross-sectional analysis of the nationally representative National Health and Nutrition Examination Surveys (NHANES) and predecessor surveys, conducted from 1959 to 2018. included 160 495 participants aged 6 to 74 years.
Family income quintile defined using year-specific thresholds; educational attainment.
Trends in socioeconomic disparities in prevalence of current/former smoking among adults aged 25 to 74 years; 3 respiratory symptoms (dyspnea on exertion, cough, and wheezing) among adults aged 40 to 74 years; asthma stratified by age (6-11, 12-17, and 18-74 years); chronic obstructive pulmonary disease (COPD adults aged 40-74 years); and 3 measures of pulmonary function (forced expiratory volume in 1 second FEV1, forced vital capacity FVC, and FEV1/FVC<0.70) among adults aged 24 to 74 years.
Our sample included 160 495 individuals surveyed between 1959 and 2018: 27 948 children aged 6 to 11 years; 26 956 children aged 12 to 17 years; and 105 591 adults aged 18 to 74 years. Income- and education-based disparities in smoking prevalence widened from 1971 to 2018. Socioeconomic disparities in respiratory symptoms persisted or worsened from 1959 to 2018. For instance, from 1971 to 1975, 44.5% of those in the lowest income quintile reported dyspnea on exertion vs 26.4% of those in the highest quintile, whereas from 2017 to 2018 the corresponding proportions were 48.3% and 27.9%. Disparities in cough and wheezing rose over time. Asthma prevalence rose for all children after 1980, but more sharply among poorer children. Income-based disparities in diagnosed COPD also widened over time, from 4.5 percentage points (age- and sex-adjusted) in 1971 to 11.3 percentage points from 2013 to 2018. Socioeconomic disparities in FEV1 and FVC also increased. For instance, from 1971 to 1975, the age- and height-adjusted FEV1 of men in the lowest income quintile was 203.6 mL lower than men in the highest quintile, a difference that widened to 248.5 mL from 2007 to 2012 (95% CI, -328.0 to -169.0). However, disparities in rates of FEV1/FVC lower than 0.70 changed little.
Socioeconomic disparities in pulmonary health persisted and potentially worsened over the past 6 decades, suggesting that the benefits of improved air quality and smoking reductions have not been equally distributed. Socioeconomic position may function as an independent determinant of pulmonary health.
Regulations on e-cigarettes in the U.S. do not provide guidelines on the chemical content of e-cigarette liquids. We evaluated emissions of aldehydes and flavoring chemicals in e-cigarette vapor ...under typical usage conditions. We selected 24 e-cigarette flavors from the top selling disposable e-cigarette brands. E-cigarettes were connected to a pump drawing air for two second puffs with sixty-second intervals between puffs. The vapor was analyzed for the presence of aldehydes using high-performance liquid chromatography-ultraviolet detector and for the presence of flavoring chemicals with gas chromatography and an electron capture detector. All e-cigarette emissions tested contained at least one aldehyde and/or flavoring chemical on either the FEMA "High Priority Chemicals" or FDA Harmful and Potentially Harmful Constituents lists when sampled at typical usage conditions. Diacetyl, a known respiratory hazard, along with acetoin, were the most prevalent of the flavoring chemicals in e-cigarette vapor, being found in more than 60% of samples. The presence of propionaldehyde, acetaldehyde and formaldehyde were correlated, corroborating previous work suggesting thermal degradation as a pathway for aldehyde generation in e-cigarette vapors. Median formaldehyde concentrations of 626 μg/m
in e-cigarette vapor exceed the ACGIH maximum concentrations allowable for workers of 370 μg/m
.
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