Prognostic Significance of Large Airway Dimensions on Computed Tomography in the General Population. The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

Rationale: Large airway dimensions on computed tomography (CT) have been associated with lung function, symptoms, and exacerbations in chronic obstructive pulmonary disease (COPD), as well as with symptoms in smokers with preserved spirometry. Their prognostic significance in persons without lung disease remains undefined.

Objectives: To examine associations between large airway dimensions on CT and respiratory outcomes in a population-based cohort of adults without prevalent lung disease.

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases.

Long-term outdoor air pollution and DNA methylation in circulating monocytes: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: DNA methylation may mediate effects of air pollution on cardiovascular disease. The association between long-term air pollution exposure and DNA methylation in monocytes, which are central to atherosclerosis, has not been studied. We investigated the association between long-term ambient air pollution exposure and DNA methylation (candidate sites and global) in monocytes of adults (aged ≥55).

Classifying Chronic Lower Respiratory Disease Events in Epidemiologic Cohort Studies.

Rationale: One in 12 adults has chronic obstructive pulmonary disease or asthma. Acute exacerbations of these chronic lower respiratory diseases (CLRDs) are a major cause of morbidity and mortality. Valid approaches to classifying cases and exacerbations in the general population are needed to facilitate prevention research.

Asthma predicts cardiovascular disease events: the multi-ethnic study of atherosclerosis.

Objectives: To identify and characterize an association between persistent asthma and cardiovascular disease (CVD) risk in the Multi-Ethnic Study of Atherosclerosis (MESA).

Approach And Results: MESA is a longitudinal prospective study of an ethnically diverse cohort of individuals free of known CVD at its inception. The presence and severity of asthma were assessed in the MESA at examination 1.

Transcriptomic profiles of aging in purified human immune cells.

Background: Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell types often make these results difficult to interpret.

Results: Using transcriptomic profiles in CD14+ monocytes from 1,264 participants of the Multi-Ethnic Study of Atherosclerosis (aged 55-94 years), we identified 2,704 genes differentially expressed with chronological age (false discovery rate, FDR ≤ 0.

Intercellular adhesion molecule 1 and progression of percent emphysema: the MESA Lung Study.

Background: Endothelial intercellular adhesion molecule (ICAM) 1 binds neutrophils and facilitates their transmigration into the lung; E-selectin facilitates leukocyte rolling. As neutrophils contribute to tissue destruction in emphysema and chronic obstructive pulmonary disease, we hypothesized that soluble ICAM-1 (sICAM-1) and E-selectin (sE-selectin) would be associated with longitudinal progression of emphysema and lung function decline.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants 45-84 years old without clinical cardiovascular disease in 2000-02.

Asthma in inner-city children at 5-11 years of age and prenatal exposure to phthalates: the Columbia Center for Children's Environmental Health Cohort.

Background: Studies suggest that phthalate exposures may adversely affect child respiratory health.

Objectives: We evaluated associations between asthma diagnosed in children between 5 and 11 years of age and prenatal exposures to butylbenzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), and diethyl phthalate (DEP).

Methods: Phthalate metabolites were measured in spot urine collected from 300 pregnant inner-city women.

Common genes underlying asthma and COPD? Genome-wide analysis on the Dutch hypothesis.

Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background ("Dutch hypothesis"). We investigated whether asthma and COPD have common underlying genetic factors, performing genome-wide association studies for both asthma and COPD and combining the results in meta-analyses. Three loci showed potential involvement in both diseases: chr2p24.

Comparison of spatially matched airways reveals thinner airway walls in COPD. The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study and the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS).

Background: COPD is characterised by reduced airway lumen dimensions and fewer peripheral airways. Most studies of airway properties sample airways based upon lumen dimension or at random, which may bias comparisons given reduced airway lumen dimensions and number in COPD. We sought to compare central airway wall dimensions on CT in COPD and controls using spatially matched airways, thereby avoiding selection bias of airways in the lung.

Occupational risk factors for COPD phenotypes in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

Introduction: The contribution of occupational exposure to the risk of chronic obstructive pulmonary disease COPD in population-based studies is of interest. We compared the performance of self-reported exposure to a newly developed JEM in exposure-response evaluation.

Methods: We used cross-sectional data from Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of 45-84 year olds free of clinical cardiovascular disease at baseline.

Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children.

Background: Bisphenol A (BPA) is used widely to manufacture food container linings. Mouse models suggest exposure to BPA might increase allergic inflammation.

Objectives: We hypothesized that BPA exposure, as assessed based on urinary BPA concentrations, would be associated with increased odds of wheeze and asthma and increased fraction of exhaled nitric oxide (Feno) values in children.

Asthma and lung structure on computed tomography: the Multi-Ethnic Study of Atherosclerosis Lung Study.

Background: The potential consequences of asthma in childhood and young adulthood on lung structure in older adults have not been studied in a large, population-based cohort.

Objective: The authors hypothesized that a history of asthma onset in childhood (age 18 years or before) or young adulthood (age 19-45 years) was associated with altered lung structure on computed tomography in later life.

Methods: The Multi-Ethnic Study of Atherosclerosis Lung Study recruited 3965 participants and assessed asthma history by using standardized questionnaires, guideline-based spirometry, and segmental airway dimensions and percentage of low attenuation area (%LAA) on computed tomographic scans.

Social factors and leukocyte DNA methylation of repetitive sequences: the multi-ethnic study of atherosclerosis.

Epigenetic changes are a potential mechanism contributing to race/ethnic and socioeconomic disparities in health. However, there is scant evidence of the race/ethnic and socioeconomic patterning of epigenetic marks. We used data from the Multi-Ethnic Study of Atherosclerosis Stress Study (N = 988) to describe age- and gender-independent associations of race/ethnicity and socioeconomic status (SES) with methylation of Alu and LINE-1 repetitive elements in leukocyte DNA.

Cigarette smoking and airway wall thickness on CT scan in a multi-ethnic cohort: the MESA Lung Study.

Background: Autopsy studies show that smoking contributes to airway wall hyperplasia and narrowing of the airway lumen. Studies of smoking and airway measures on computed tomography (CT) scan are limited to case-control studies of measures that combine airway lumen and wall thickness.

Objectives: We hypothesized that cumulative cigarette smoking would be associated with increased airway wall thickness in a large, population-based cohort.

Anti-cockroach and anti-mouse IgE are associated with early wheeze and atopy in an inner-city birth cohort.

Background: The relationships between cockroach and mouse allergen exposure, anti-cockroach and anti-mouse IgE, and wheeze, rhinitis, and atopic dermatitis in children as young as age 3 years are of public health importance but have not been thoroughly evaluated.

Objective: We hypothesized that inner-city children might have anti-cockroach and anti-mouse IgE by age 3 years, and their presence would be associated with respiratory and atopic symptoms.

Methods: Children were followed prospectively from birth through age 3 years (n = 404).

Chemotherapy agents and timing of chemotherapy in prostate cancer management.

In 2005, it is estimated that more than 30,000 men will die from metastatic hormone-refractory prostate cancer. For decades, no chemotherapeutic agent demonstrated a survival benefit in these patients, although two randomized clinical trials demonstrated a clear palliative benefit using mitoxantrone combined with a corticosteroid. However, beginning in 1999, a series of phase-2 trials were performed using docetaxel, either as a single agent or in combination with estramustine.