Suh MacIntosh, Helen H.

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Suh MacIntosh, Helen H.

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Suh MacIntosh

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Helen H.

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Suh MacIntosh, Helen H.

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A Novel Genetic Score Approach Using Instruments to Investigate Interactions between Pathways and Environment: Application to Air Pollution
(Public Library of Science, 2014) Bind, Marie-Abele; Coull, Brent; Suh MacIntosh, Helen H.; Wright, Robert; Baccarelli, Andrea; Vokonas, Pantel; Schwartz, Joel
Air pollution has been associated with increased systemic inflammation markers. We developed a new pathway analysis approach to investigate whether gene variants within relevant pathways (oxidative stress, endothelial function, and metal processing) modified the association between particulate air pollution and fibrinogen, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). Our study population consisted of 822 elderly participants of the Normative Aging Study (1999–2011). To investigate the role of biological mechanisms and to reduce the number of comparisons in the analysis, we created pathway-specific scores using gene variants related to each pathway. To select the most appropriate gene variants, we used the least absolute shrinkage and selection operator (Lasso) to relate independent outcomes representative of each pathway (8-hydroxydeoxyguanosine for oxidative stress, augmentation index for endothelial function, and patella lead for metal processing) to gene variants. A high genetic score corresponds to a higher allelic risk profile. We fit mixed-effects models to examine modification by the genetic score of the weekly air pollution association with the outcome. Among participants with higher genetic scores within the oxidative stress pathway, we observed significant associations between particle number and fibrinogen, while we did not find any association among participants with lower scores (pinteraction = 0.04). Compared to individuals with low genetic scores of metal processing gene variants, participants with higher scores had greater effects of particle number on fibrinogen (pinteraction = 0.12), CRP (pinteraction = 0.02), and ICAM-1 (pinteraction = 0.08). This two-stage penalization method is easy to implement and can be used for large-scale genetic applications.
Opposing Effects of Particle Pollution, Ozone, and Ambient Temperature on Arterial Blood Pressure
(National Institute of Environmental Health Sciences, 2012) Luttmann-Gibson, Heike; de Souza, Celine; Foley, Christopher; Hoffmann, Barbara H.; Cohen, Allison; Zanobetti, Antonella; Suh MacIntosh, Helen H.; Coull, Brent; Schwartz, Joel; Mittleman, Murray; Stone, Peter; Horton, Edward; Gold, Diane
Background: Diabetes increases the risk of hypertension and orthostatic hypotension and raises the risk of cardiovascular death during heat waves and high pollution episodes. Objective: We examined whether short-term exposures to air pollution (fine particles, ozone) and heat resulted in perturbation of arterial blood pressure (BP) in persons with type 2 diabetes mellitus (T2DM). Methods: We conducted a panel study in 70 subjects with T2DM, measuring BP by automated oscillometric sphygmomanometer and pulse wave analysis every 2 weeks on up to five occasions (355 repeated measures). Hourly central site measurements of fine particles, ozone, and meteorology were conducted. We applied linear mixed models with random participant intercepts to investigate the association of fine particles, ozone, and ambient temperature with systolic, diastolic, and mean arterial BP in a multipollutant model, controlling for season, meteorological variables, and subject characteristics. Results: An interquartile increase in ambient fine particle mass [particulate matter (PM) with an aerodynamic diameter of \(\leq\) 2.5 \(\mu\)m (PM\(_{2.5}\))] and in the traffic component black carbon in the previous 5 days (3.54 and 0.25 \(\mu\)g/m\(^3\), respectively) predicted increases of 1.4 mmHg [95% confidence interval (CI): 0.0, 2.9 mmHg] and 2.2 mmHg (95% CI: 0.4, 4.0 mmHg) in systolic BP (SBP) at the population geometric mean, respectively. In contrast, an interquartile increase in the 5-day mean of ozone (13.3 ppb) was associated with a 5.2 mmHg (95% CI: –8.6, –1.8 mmHg) decrease in SBP. Higher temperatures were associated with a marginal decrease in BP. Conclusions: In subjects with T2DM, PM was associated with increased BP, and ozone was associated with decreased BP. These effects may be clinically important in patients with already compromised autoregulatory function.
Effects of Ambient Air Pollution on Functional Status in Patients with Chronic Congestive Heart Failure: a Repeated-Measures Study
(BioMed Central, 2007) Wellenius, Gregory A.; Yeh, Gloria; Coull, Brent; Suh MacIntosh, Helen H.; Phillips, Russell; Mittleman, Murray
Background: Studies using administrative data report a positive association between ambient air pollution and the risk of hospitalization for congestive heart failure (HF). Circulating levels of B-type natriuretic peptide (BNP) are directly associated with cardiac hemodynamics and symptom severity in patients with HF and, therefore, serves as a marker of functional status. We tested the hypothesis that BNP levels would be positively associated with short-term changes in ambient pollution levels among 28 patients with chronic stable HF and impaired systolic function. Methods: BNP was measured in whole blood at 0, 6, and 12 weeks. We used linear mixed models to evaluate the association between fine particulate matter (PM2.5), carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, and black carbon and log(BNP). Lags of 0 to 3 days were considered in separate models. We calculated the intraclass correlation coefficient and within-subject coefficient of variation as measures of reproducibility. Results: We found no association between any pollutant and measures of BNP at any lag. For example, a 10 μg/m3 increase in PM2.5 was associated with a 0.8% (95% CI: -16.4, 21.5; p = 0.94) increase in BNP on the same day. The within-subject coefficient of variation was 45% on the natural scale and 9% on the log scale. Conclusion: These results suggest that serial BNP measurements are unlikely to be useful in a longitudinal study of air pollution-related acute health effects. The magnitude of expected ambient air pollution health effects appears small in relation to the considerable within-person variability in BNP levels in this population.
Predicting Chronic Fine and Coarse Particulate Exposures Using Spatiotemporal Models for the Northeastern and Midwestern United States
(National Institute of Environmental Health Sciences, 2008) Yanosky, Jeff D.; Suh MacIntosh, Helen H.; Paciorek, Christopher Joseph
Background: Chronic epidemiologic studies of particulate matter (PM) are limited by the lack of monitoring data, relying instead on citywide ambient concentrations to estimate exposures. This method ignores within-city spatial gradients and restricts studies to areas with nearby monitoring data. This lack of data is particularly restrictive for fine particles (PM with aerodynamic diameter < 2.5 μm; PM2.5) and coarse particles (PM with aerodynamic diameter 2.5–10 μm; PM10–2.5), for which monitoring is limited before 1999. To address these limitations, we developed spatiotemporal models to predict monthly outdoor PM2.5 and PM10–2.5 concentrations for the northeastern and midwestern United States. Methods: For PM2.5, we developed models for two periods: 1988–1998 and 1999–2002. Both models included smooth spatial and regression terms of geographic information system-based and meteorologic predictors. To compensate for sparse monitoring data, the pre-1999 model also included predicted PM10 (PM with aerodynamic diameter < 10 μm) and extinction coefficients (km−1). PM10–2.5 levels were estimated as the difference in monthly predicted PM10 and PM2.5, with predicted PM10 from our previously developed PM10 model. Results: Predictive performance for PM2.5 was strong (cross-validation R2 = 0.77 and 0.69 for post-1999 and pre-1999 PM2.5 models, respectively) with high precision (2.2 and 2.7 μg/m3, respectively). Models performed well irrespective of population density and season. Predictive performance for PM10–2.5 was weaker (cross-validation R2 = 0.39) with lower precision (5.5 μg/m3). PM10–2.5 levels exhibited greater local spatial variability than PM10 or PM2.5, suggesting that PM2.5 measurements at ambient monitoring sites are more representative for surrounding populations than for PM10 and especially PM10–2.5. Conclusions: We provide semiempirical models to predict spatially and temporally resolved long-term average outdoor concentrations of PM2.5 and PM10–2.5 for estimating exposures of populations living in the northeastern and midwestern United States.
Ambient and Microenvironmental Particles and Exhaled Nitric Oxide Before and After a Group Bus Trip
(National Institute of Environmental Health Sciences, 2007) Adar, Sara Dubowsky; Adamkiewicz, Gary; Gold, Diane; Schwartz, Joel; Coull, Brent; Suh MacIntosh, Helen H.
Objectives: Airborne particles have been linked to pulmonary oxidative stress and inflammation. Because these effects may be particularly great for traffic-related particles, we examined associations between particle exposures and exhaled nitric oxide (FENO) in a study of 44 senior citizens, which involved repeated trips aboard a diesel bus. Methods: Samples of FENO collected before and after the trips were regressed against microenvironmental and ambient particle concentrations using mixed models controlling for subject, day, trip, vitamins, collection device, mold, pollen, room air nitric oxide, apparent temperature, and time to analysis. Although ambient concentrations were collected at a fixed location, continuous group-level personal samples characterized microenvironmental exposures throughout facility and trip periods. Results: In pre-trip samples, both microenvironmental and ambient exposures to fine particles were positively associated with FENO. For example, an interquartile increase of 4 μg/m3 in the daily microenvironmental PM2.5 concentration was associated with a 13% [95% confidence interval (CI), 2–24%) increase in FENO. After the trips, however, FENO concentrations were associated pre-dominantly with microenvironmental exposures, with significant associations for concentrations measured throughout the whole day. Associations with exposures during the trip also were strong and statistically significant with a 24% (95% CI, 15–34%) increase in FENO predicted per interquartile increase of 9 μg/m3 in PM2.5. Although pre-trip findings were generally robust, our post-trip findings were sensitive to several influential days. Conclusions: Fine particle exposures resulted in increased levels of FENO in elderly adults, suggestive of increased airway inflammation. These associations were best assessed by microenvironmental exposure measurements during periods of high personal particle exposures.
Effect Modification of Air Pollution on Urinary 8-Hydroxy-2'-Deoxyguanosine by Genotypes: An Application of the Multiple Testing Procedure to Identify Significant SNP Interactions
(BioMed Central, 2010) Ren, Cizao; Vokonas, Pantel; Suh MacIntosh, Helen H.; Fang, Shona C; Christiani, David; Schwartz, Joel
Background: Air pollution is associated with adverse human health, but mechanisms through which pollution exerts effects remain to be clarified. One suggested pathway is that pollution causes oxidative stress. If so, oxidative stress-related genotypes may modify the oxidative response defenses to pollution exposure. Methods: We explored the potential pathway by examining whether an array of oxidative stress-related genes (twenty single nucleotide polymorphisms, SNPs in nine genes) modified associations of pollutants (organic carbon (OC), ozone and sulfate) with urinary 8-hydroxy-2-deoxygunosine (8-OHdG), a biomarker of oxidative stress among the 320 aging men. We used a Multiple Testing Procedure in R modified by our team to identify the significance of the candidate genes adjusting for a priori covariates. Results: We found that glutathione S-tranferase P1 (GSTP1, rs1799811), M1 and catalase (rs2284367) and group-specific component (GC, rs2282679, rs1155563) significantly or marginally significantly modified effects of OC and/or sulfate with larger effects among those carrying the wild type of GSTP1, catalase, non-wild type of GC and the non-null of GSTM1. Conclusions: Polymorphisms of oxidative stress-related genes modified effects of OC and/or sulfate on 8-OHdG, suggesting that effects of OC or sulfate on 8-OHdG and other endpoints may be through the oxidative stress pathway.
Workgroup Report: Workshop on Source Apportionment of Particulate Matter Health Effects—Intercomparison of Results and Implications
(National Institute of Environmental Health Sciences, 2005) Thurston, George D.; Ito, Kazuhiko; Mar, Therese; Christensen, William F.; Eatough, Delbert J.; Henry, Ronald C.; Lall, Ramona; Larson, Timothy V.; Neas, Lucas; Pinto, Joseph; Stölzel, Matthias; Hopke, Philip K.; Kim, Eugene; Laden, Francine; Liu, Hao; Suh MacIntosh, Helen H.
Although the association between exposure to ambient fine particulate matter with aerodynamic diameter < 2.5 μm (PM\(_{2.5}\)) and human mortality is well established, the most responsible particle types/sources are not yet certain. In May 2003, the U.S. Environmental Protection Agency’s Particulate Matter Centers Program sponsored the Workshop on the Source Apportionment of PM Health Effects. The goal was to evaluate the consistency of the various source apportionment methods in assessing source contributions to daily PM\(_{2.5}\) mass–mortality associations. Seven research institutions, using varying methods, participated in the estimation of source apportionments of PM\(_{2.5}\) mass samples collected in Washington, DC, and Phoenix, Arizona, USA. Apportionments were evaluated for their respective associations with mortality using Poisson regressions, allowing a comparative assessment of the extent to which variations in the apportionments contributed to variability in the source-specific mortality results. The various research groups generally identified the same major source types, each with similar elemental makeups. Intergroup correlation analyses indicated that soil-, sulfate-, residual oil-, and salt-associated mass were most unambiguously identified by various methods, whereas vegetative burning and traffic were less consistent. Aggregate source-specific mortality relative risk (RR) estimate confidence intervals overlapped each other, but the sulfate-related PM\(_{2.5}\) component was most consistently significant across analyses in these cities. Analyses indicated that source types were a significant predictor of RR, whereas apportionment group differences were not. Variations in the source apportionments added only some 15% to the mortality regression uncertainties. These results provide supportive evidence that existing PM\(_{2.5}\) source apportionment methods can be used to derive reliable insights into the source components that contribute to PM\(_{2.5}\) health effects.
Black Carbon Exposure, Oxidative Stress Genes, and Blood Pressure in a Repeated-measures Study
(National Institute of Environmental Health Sciences, 2009) Mordukhovich, Irina; Wilker, Elissa; Suh MacIntosh, Helen H.; Wright, Robert; Sparrow, David; Vokonas, Pantel; Schwartz, Joel
Background: Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests that traffic-related air pollution contributes significantly to PM-related cardiovascular effects. Objectives: We hypothesized that black carbon (BC), a traffic-related combustion by-product, would be more strongly associated with BP than would fine PM [aerodynamic diameter ≤ 2.5 μm (PM\(_{2.5}\))], a heterogeneous PM mixture, and that these effects would be larger among participants with genetic variants associated with impaired antioxidative defense. Methods: We performed a repeated-measures analysis in elderly men to analyze associations between PM\(_{2.5}\) and BC exposure and BP using mixed-effects models with random intercepts, adjusting for potential confounders. We also examined statistical interaction between BC and genetic variants related to oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1. Results: A 1-SD increase in BC concentration was associated with a 1.5-mmHg increase in systolic BP [95% confidence interval (CI), 0.1–2.8] and a 0.9-mmHg increase in diastolic BP (95% CI, 0.2–1.6). We observed no evidence of statistical interaction between BC and any of the genetic variants examined and found no association between PM\(_{2.5}\) and BP. Conclusions: We observed positive associations between BP and BC, but not between BP and PM\(_{2.5}\), and found no evidence of effect modification of the association between BC and BP by gene variants related to antioxidative defense.
The Relationship Between Ambient Air Pollution and Heart Rate Variability Differs for Individuals with Heart and Pulmonary Disease
(National Institute of Environmental Health Sciences, 2005) Wheeler, Amanda; Zanobetti, Antonella; Gold, Diane; Schwartz, Joel; Stone, Peter; Suh MacIntosh, Helen H.
Associations between concentrations of ambient fine particles [particulate matter < 2.5 μm aerodynamic diameter (PM\(_{2.5}\))] and heart rate variability (HRV) have differed by study population. We examined the effects of ambient pollution on HRV for 18 individuals with chronic obstructive pulmonary disease (COPD) and 12 individuals with recent myocardial infarction (MI) living in Atlanta, Georgia. HRV, baseline pulmonary function, and medication data were collected for each participant on 7 days in fall 1999 and/or spring 2000. Hourly ambient pollution concentrations were obtained from monitoring sites in Atlanta. The association between ambient pollution and HRV was examined using linear mixed-effect models. Ambient pollution had opposing effects on HRV in our COPD and MI participants, resulting in no significant effect of ambient pollution on HRV in the entire population for 1-, 4-, or 24-hr moving averages. For individuals with COPD, interquartile range (IQR) increases in 4-hr ambient PM\(_{2.5}\) (11.65 μg/m\(^3\)) and nitrogen dioxide (11.97 ppb) were associated with 8.3% [95% confidence interval (CI), 1.7–15.3%] and 7.7% (95% CI, 0.1–15.9%) increase in the SD of normal R-R intervals (SDNN), respectively. For individuals with MI, IQR increases in 4-hr PM\(_{2.5}\) (8.54 μg/m\(^3\)) and NO2 (9.25 ppb) were associated with a nonsignificant 2.9% (95% CI, –7.8 to 2.3) and significant 12.1 (95% CI, –19.5 to –4.0) decrease in SDNN. Beta-blocker and bronchodilator intake and baseline forced expiratory volume in 1 sec modified the PM–SDNN association significantly, with effects consistent with those by disease group. Results indicate heterogeneity in the autonomic response to air pollution due to differences in baseline health, with significant associations for ambient NO2 suggesting an important role for traffic-related pollution.
Chronic Fine and Coarse Particulate Exposure, Mortality, and Coronary Heart Disease in the Nurses’ Health Study
(National Institute of Environmental Health Sciences, 2009) Puett, Robin C.; Yanosky, Jeff D; Hart, Jaime; Paciorek, Christopher Joseph; Schwartz, Joel; Suh MacIntosh, Helen H.; Speizer, Frank; Laden, Francine
Background: The relationship of fine particulate matter < 2.5 μm in diameter (PM2.5) air pollution with mortality and cardiovascular disease is well established, with more recent long-term studies reporting larger effect sizes than earlier long-term studies. Some studies have suggested the coarse fraction, particles between 2.5 and 10 μm (PM10–2.5), may also be important. With respect to mortality and cardiovascular events, questions remain regarding the relative strength of effect sizes for chronic exposure to fine and coarse particles. Objectives: We examined the relationship of chronic PM2.5 and PM10–2.5 exposures with all-cause mortality and fatal and nonfatal incident coronary heart disease (CHD), adjusting for time-varying covariates. Methods: The current study included women from the Nurses’ Health Study living in metropolitan areas of the northeastern and midwestern United States. Follow-up was from 1992 to 2002. We used geographic information systems–based spatial smoothing models to estimate monthly exposures at each participant’s residence. Results: We found increased risk of all-cause mortality [hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.02–1.54] and fatal CHD (HR = 2.02; 95% CI, 1.07–3.78) associated with each 10-μg/m3 increase in annual PM2.5 exposure. The association between fatal CHD and PM10–2.5 was weaker. Conclusions: Our findings contribute to growing evidence that chronic PM2.5 exposure is associated with risk of all-cause and cardiovascular mortality.