Epidemiology & Biostatistics
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Item Allostatic load amplifies the effect of blood lead levels on elevated blood pressure among middle-aged U.S. adults: a cross-sectional study(Springer Nature, 2013-08-16) Zota, Ami R; Shenassa, Edmond D; Morello-Frosch, RachelScientists and regulators have sought to understand whether and how physiologic dysregulation due to chronic stress exposure may enhance vulnerability to the adverse health effects of toxicant exposures. We conducted a cross-sectional study to determine whether allostatic load (AL), a composite measure of physiologic response to chronic exposure to stress, amplifies the effect of lead exposure on blood pressure among middle-aged adults. We analyzed associations between blood lead levels and blood pressure in a nationally representative sample of 8,194 U.S. adults (aged 40-65 years) participating in the National Health and Nutritional Examination Survey, 1999--2008. Outcomes were elevated systolic (≥ 140 mm Hg) and diastolic (≥ 90 mm Hg) blood pressure. AL was defined as the aggregate score of seven components, reflecting dysregulation of the cardiovascular, inflammatory, and endocrine systems. Logistic regression models showed a linear dose-response relationship for quintiles of blood lead and elevated systolic blood pressure in the high AL group (p = 0.03) but not the low AL group (p = 0.24). Similarly, the relationship between lead exposure and elevated diastolic blood pressure was stronger among the high AL group than the low AL group. Within the high AL group, the fourth and fifth quintiles had significantly elevated odds of elevated blood pressure compared to lowest quintile [OR = 1.92, (95% CI, 1.07, 3.47) and OR =2.28 (95% CI, 1.33, 3.91), respectively]. In the low AL group, none of the quintile effects were significantly different than the referent group although there was evidence of a linear trend (p =0.03). The lead by AL interaction term was not statistically significant for either systolic or diastolic blood pressure models. Results suggest that higher AL may amplify the adverse effects of lead on blood pressure. Future research should assess the implications of cumulative exposures to environmental and social stressors for regulatory decision-making.Item ESTIMATING RISK OF AIRBORNE INFLUENZA TRANSMISSION IN A CONTROLLED ENVIRONMENT(2019) Bueno de Mesquita, Paul Jacob; Milton, Donald K.; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Pandemic preparedness is weakened by uncertainty about the relative importance of influenza transmission modes, particularly airborne droplet nuclei (aerosols). A human-challenge transmission trial in a controlled environment was conducted to address this uncertainty. Healthy, seronegative volunteer ‘Donors’ (N=52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2) and exposed to seronegative ‘Recipients’ randomized to intervention (N=40) or control (N=35) groups. Intervention recipients wore face shields and hand sanitized frequently to limit large droplet and contact transmission. A transmitted infection, confirmed by serology in a control recipient, yielded a 1.3% SAR overall. This was significantly less than the expected 16% SAR (p <0.001) based on a proof-of-concept study that used half as many Donors and exposure days. The main difference between these studies was mechanical building ventilation in the follow-on study, suggesting a possible role for aerosols. The extent to which Donor viral shedding was similar to that of mild, natural infections and may be useful for studying transmission was investigated. The only available aerosol shedding comparison data comes from a population of adults with influenza A H3 infection enrolled on the basis of febrile illness plus cough or sore throat, or positive Quidel QuickVue rapid test (N=83). Systematic differences in case selection compared with Donors yielded more severe cases and introduced bias. To account for differences in illness severity, propensity score matching, stratification, and inverse weighting ultimately demonstrated that the experimental and naturally infected groups were too different to compare without bias. While acknowledging the uncertainty in the generalizability of the current challenge model, observed aerosol shedding and CO2 were used in the rebreathed-air version of the Wells-Riley equation to compute average quantum generation rates (95% CI) 0.029 (0.027, 0.03) and 0.11 (0.088, 0.12) per hour for infected Donors and fine aerosol shedding Donors, respectively. Donors shed 1.4E+5 (1.0E+5, 1.8E+5) airborne viral RNA copies per quantum (ID63). This dissertation provides evidence for airborne transmission, presents a methodology for estimating an airborne dose, and suggests a role for building ventilation in reducing risk and the need for future observational studies to evaluate transmission modes in non-experimental settings with greater generalizability.Item Relationships of social and physical environmental factors with cardiometabolic outcomes(2019) Huang, Dina; Puett, Robin; Nguyen, Quynh C; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The social and physical environmental factors impact health in general and have been linked with increased risks of cardiometabolic outcomes including obesity, diabetes, hypertension and cardiometabolic biomarkers. The dissertation added to important knowledge on this topic in two ways: 1) by leveraging innovative Twitter-derived characteristics to study the potential influence of social environment on cardiometabolic outcomes, 2) investigating the effects of air pollution exposures on cardiometabolic outcomes in youth living with type I diabetes. The first study investigated the associations between Twitter-derived area-level predictors (happiness, diet, physical activity) with cardiometabolic outcomes (obesity, diabetes, hypertension) using a nationally representative sample from National Health and Nutrition Examination Survey (NHANES). People living in neighborhoods with higher happiness, healthier diet and more physical activity had lower prevalence of obesity and hypertension but not diabetes. Twitter-derived social neighborhood characteristics can be used to identify communities with higher risk of cardiometabolic outcomes. We obtained data from SEARCH for Diabetes in Youth (SEARCH) study for the second and the third study. The second study examined the associations between chronic exposure to air pollution and glucose hemostasis (HbA1c) in youth living with type I diabetes. Particulate matter with aerodynamic diameter <2.5 (PM2.5), proximity to heavily trafficked roads and annual average daily traffic count were associated with higher HbA1c in study site South Carolina, Colorado and Washington, but not in study site Ohio and California. Differences in particulate matter compositions may explain the inconsistent results. The third study assessed the effect of acute exposure to air pollution on subclinical CVD markers including pulse wave velocity (PWV), augmentation index (AIx) and brachial distensibility (BrachD) using a repeated measures design. Reduction in PM2.5 on the day prior to assessment was associated with lower AIx, but not associated with either PWV or BrachD. In summary, exposure to air pollution may be associated with cardiometabolic outcomes and reducing air pollution may have implications in early prevention of cardiovascular complications for youth living with type I diabetes. Overall, reducing social stressors and reducing hazardous physical environmental factors may decrease the risk of cardiometabolic outcomes, providing possible directions for CVD prevention for public health practitioners.Item ASSOCIATIONS BETWEEN AMBIENT PARTICULATE MATTER EXPOSURES, STROKE, AND MARKERS OF CARDIOVASCULAR INFLAMMATION(2017) Fisher, Jared A.; Puett, Robin C; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Stroke is a leading cause of morbidity and mortality in the United States with 795,000 people experiencing a new or recurrent stroke every year. Identifying modifiable risk factors for stroke should therefore be considered a research priority. While associations between ambient exposure to air pollution and other cardiovascular diseases are well established in the literature, the evidence linking particulate matter (PM) air pollution exposures to the risk of ischemic or hemorrhagic stroke remains equivocal. Furthermore, the exact pathophysiologic mechanisms by which exposure to PM may lead to cerebrovascular events are not yet fully understood. Hypothesized pathways include the mediation of effects through a combination of inflammatory responses, autonomic dysregulation, and/or vascular endothelial disturbances. This dissertation addresses existing gaps in the literature in three separate studies. Two time-stratified case-crossover studies examined the association between short-term PM exposures and stroke risk, one in the Health Professionals Follow-up Study (HPFS) and the other among a large database of Maryland stroke hospitalizations. Conditional logistic regression models were used to examine associations by stroke subtype, population subgroups, and clinically-relevant variables. Our third study took place within the Nurses’ Health Study cohort. Multivariable linear regression models were used to examine the associations between PM and residential distance to road exposures and four inflammatory biomarkers (CRP, IL-6, fibrinogen, and ICAM-1). We found positive significant associations between PM10 and ischemic stroke events in the HPFS cohort, and associations were elevated for nonsmokers, aspirin nonusers, and those without a history of high cholesterol. Concentrations were elevated for both CRP and IL-6 among participants who lived close to a major roadway, but no significant results were found by estimated PM exposure. This work provides additional evidence that PM exposure is associated with ischemic stroke and adds to the current literature that those not currently taking aspirin and those without a history of high cholesterol may be at elevated risk. Although the direct role of inflammatory processes requires more investigation, this work does provide additional evidence that proximity to traffic may influence cardiovascular-related inflammation.Item Associations between Urinary Phthalates and Metabolic Syndrome in NHANES 2005-2010(2015) Haque, Mefruz Salwa; Dallal, Cher M; Epidemiology and Biostatistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Phthalates, commonly used to make plastics more durable, are a group of endocrine disrupting chemicals (EDC), with potential for adverse metabolic consequences. Associations between exposure to 13 phthalate metabolites and the prevalence of metabolic syndrome (MetS) were examined among 5,409 U.S adults ≥ 18 years of age, who participated in the National Health and Nutrition Examination Survey from 2005-2010. MetS was assessed using clinical and questionnaire data. Odds Ratio (OR) and 95% Confidence Intervals (CI) adjusting for age, creatinine and key confounders, were estimated with multivariable logistic regression. Positive associations were observed between individual phthalate metabolites and MetS: (MCOP OR=1.31, 95% CI=1.40, 1.64, p-trend<.01; MCPP OR=1.39, 95% CI=1.09, 1.77, p-trend=0.01). In gender stratified analyses, findings with MCOPP and MCPP were restricted to women only. Phthalate metabolites may increase the prevalence of MetS; however, further studies are needed to better understand the role of EDCs in the development of MetS.