Jaime Madrigano

Prolonged exposure to particulate pollution, genes associated with glutathione pathways, and DNA methylation in a cohort of older men

Background: DNA methylation is a potential pathway linking environmental exposures to disease. Exposure to particulate air pollution has been associated with increased cardiovascular morbidity and mortality, and lower blood DNA methylation has been found in processes related to cardiovascular morbidity. Objective: We hypothesized that prolonged exposure to particulate pollution would be associated with hypomethylation of repetitive DNA elements and that this association would be modified by genes involved in glutathione metabolism and other host characteristics. Methods: DNA methylation of the long interspersed nucleotide element–1 (LINE-1) and the short interspersed nucleotide element Alu were measured by quantitative polymerase chain reaction pyrosequencing in 1,406 blood samples from 706 elderly participants in the Normative Aging Study. We estimated changes in repetitive element DNA methylation associated with ambient particles (particulate matter ≤ 2.5 µm in aerodynamic diameter), black carbon (BC), and sulfates (SO4), with mixed models. We examined multiple exposure windows (1–6 months) before DNA methylation measurement. We investigated whether this association was modified by genotype and phenotype. Results: An interquartile range (IQR) increase in BC over a 90-day period was associated with a decrease of 0.31% 5-methylcytosine (5mC) (95% confidence interval, 0.12–0.50%) in Alu. An IQR increase in SO4 over a 90-day period was associated with a decrease of 0.27% 5mC (0.02–0.52%) in LINE-1. The glutathione S-transferase mu-1–null genotype strengthened the association between BC and Alu hypomethylation. Conclusion: Prolonged exposure to BC and SO4 particles was associated with hypomethylation of two types of repetitive elements.

Aging and epigenetics : longitudinal changes in gene-specific DNA methylation

DNA methylation has been associated with age-related disease. Intra-individual changes in gene-specific DNA methylation over time in a community-based cohort has not been well described. We estimated the change in DNA methylation due to aging for nine genes in an elderly, community-dwelling cohort of men. Seven hundred and eighty four men from the Veterans Administration Normative Aging Study who were living in metropolitan Boston from 1999–2009 donated a blood sample for DNA methylation analysis at clinical examinations repeated at approximately 3-5 year intervals. We used mixed effects regression models. Aging was significantly associated with decreased methylation of GCR, iNOS and TLR2 and with increased methylation of IFNγ, F3, CRAT and OGG. Obstructive pulmonary disease at baseline modified the effect of aging on methylation of IFNγ (interaction p = 0.04). For participants who had obstructive pulmonary disease at their baseline visit, the rate of change of methylation of IFNγ was -0.05% 5-methyl-cytosine (5-mC) per year (95% CI: -0.22, 0.13), but was 0.14% 5-mC per year (95% CI: 0.05, 0.24) for those without this condition. Models with random slopes indicated significant heterogeneity in the effect of aging on methylation of GCR, iNOS and OGG. These findings suggest that DNA methylation may reflect differential biological aging.

Air Pollution, Obesity, Genes, and Cellular Adhesion Molecules

Objectives Particulate matter has been associated with acute cardiovascular outcomes, but our understanding of the mechanism is incomplete. We examined the association between particulate matter and cell adhesion molecules. We also investigated the modifying effect of genotype and phenotype variation to gain insight into the relevant biological pathways for this association. Methods We used mixed regression models to examine the association of PM2.5 (particulate matter ≤2.5 μm in diameter) and black carbon with serum concentrations of soluble intercellular adhesion molecule (sICAM-1) and soluble vascular cell adhesion molecule (sVCAM-1), markers of endothelial function and inflammation, in a longitudinal study of 809 participants in the Normative Ageing Study (1819 total observations). We also examined whether this association was modified by genotype, obesity or diabetes status. Genes selected for analyses were either related to oxidative stress, endothelial function, lipid metabolism or metal processing. Results Black carbon during the 2 days prior to blood draw was significantly associated with increased sVCAM-1 (4.5% increase per 1 μg/m3, 95% CI 1.1 to 8.0). Neither pollutant was associated with sICAM-1. Larger effects of black carbon on sVCAM were seen in subjects with obesity (p=0.007) and who were GSTM1 null (p=0.02). Conclusions Black carbon is associated with markers of endothelial function and inflammation. Genes related to oxidative defence may modify this association.

Temperature, Myocardial Infarction, and Mortality: Effect Modification by Individual and Area-Level Characteristics

Background: Although several studies have examined associations between temperature and cardiovascular-disease-related mortality, fewer have investigated the association between temperature and the development of acute myocardial infarction (MI). Moreover, little is known about who is most susceptible to the effects of temperature. Methods: We analyzed data from the Worcester Heart Attack Study, a community-wide investigation of acute MI in residents of the Worcester (MA) metropolitan area. We used a case-crossover approach to examine the association of apparent temperature with acute MI occurrence and with all-cause in-hospital and postdischarge mortality. We examined effect modification by sociodemographic characteristics, medical history, clinical complications, and physical environment. Results: A decrease in an interquartile range in apparent temperature was associated with an increased risk of acute MI on the same day (hazard ratio = 1.15 [95% confidence interval = 1.01–1.31]). Extreme cold during the 2 days prior was associated with an increased risk of acute MI (1.36 [1.07–1.74]). Extreme heat during the 2 days prior was also associated with an increased risk of mortality (1.44 [1.06–1.96]). Persons living in areas with greater poverty were more susceptible to heat. Conclusions: Exposure to cold increased the risk of acute MI, and exposure to heat increased the risk of dying after an acute MI. Local area vulnerability should be accounted for as cities prepare to adapt to weather fluctuations as a result of climate change.

Long-term exposure to PM2.5 and incidence of acute myocardial infarction.

Background: A number of studies have shown associations between chronic exposure to particulate air pollution and increased mortality, particularly from cardiovascular disease, but fewer studies have examined the association between long-term exposure to fine particulate air pollution and specific cardiovascular events, such as acute myocardial infarction (AMI). Objective: We examined how long-term exposure to area particulate matter affects the onset of AMI, and we distinguished between area and local pollutants. Methods: Building on the Worcester Heart Attack Study, an ongoing community-wide investigation examining changes over time in myocardial infarction incidence in greater Worcester, Massachusetts, we conducted a case–control study of 4,467 confirmed cases of AMI diagnosed between 1995 and 2003 and 9,072 matched controls selected from Massachusetts resident lists. We used a prediction model based on satellite aerosol optical depth (AOD) measurements to generate both exposure to particulate matter ≤ 2.5 μm in diameter (PM2.5) at the area level (10 × 10 km) and the local level (100 m) based on local land use variables. We then examined the association between area and local particulate pollution and occurrence of AMI. Results: An interquartile range (IQR) increase in area PM2.5 (0.59 μg/m3) was associated with a 16% increase in the odds of AMI (95% CI: 1.04, 1.29). An IQR increase in total PM2.5 (area + local, 1.05 μg/m3) was weakly associated with a 4% increase in the odds of AMI (95% CI: 0.96, 1.11). Conclusions: Residential exposure to PM2.5 may best be represented by a combination of area and local PM2.5, and it is important to consider spatial gradients within a single metropolitan area when examining the relationship between particulate matter exposure and cardiovascular events.

Air Pollution and DNA Methylation: Interaction by Psychological Factors in the VA Normative Aging Study

DNA methylation is a potential pathway linking air pollution to disease. Studies indicate that psychological functioning modifies the association between pollution and morbidity. The authors estimated the association of DNA methylation with ambient particulate matter less than 2.5 µm in diameter (PM(2.5)) and black carbon, using mixed models. DNA methylation of the inducible nitric oxide synthase gene, iNOS, and the glucocorticoid receptor gene, GCR, was measured by quantitative polymerase chain reaction pyrosequencing of 1,377 blood samples from 699 elderly male participants in the VA Normative Aging Study (1999-2009). The authors also investigated whether this association was modified by psychological factors including optimism or pessimism, anxiety, and depression. iNOS methylation was decreased after acute exposure to both black carbon and PM(2.5). A 1-μg/m(3) increase in exposure to black carbon in the 4 hours preceding the clinical examination was associated with a 0.9% decrease in 5-methylcytosine (95% CI: 0.4, 1.4) in iNOS, and a 10-μg/m(3) increase in exposure to PM(2.5) was associated with a 0.6% decrease in 5-methylcytosine (95% CI: 0.03, 1.1) in iNOS. Participants with low optimism and high anxiety had associations that were 3-4 times larger than those with high optimism or low anxiety. GCR methylation was not associated with particulate air pollution exposure.

A Case-Only Study of Vulnerability to Heat Wave-Related Mortality in New York City (2000-2011).

Background As a result of climate change, the frequency of extreme temperature events is expected to increase, and such events are associated with increased morbidity and mortality. Vulnerability patterns, and corresponding adaptation strategies, are most usefully conceptualized at a local level. Methods We used a case-only analysis to examine subject and neighborhood characteristics that modified the association between heat waves and mortality. All deaths of New York City residents from 2000 through 2011 were included in this analysis. Meteorological data were obtained from the National Climatic Data Center. Modifying characteristics were obtained from the death record and geographic data sets. Results A total of 234,042 adult deaths occurred during the warm season of our study period. Compared with other warm-season days, deaths during heat waves were more likely to occur in black (non-Hispanic) individuals than other race/ethnicities [odds ratio (OR) = 1.08; 95% CI: 1.03, 1.12], more likely to occur at home than in institutions and hospital settings (OR = 1.11; 95% CI: 1.06, 1.16), and more likely among those living in census tracts that received greater public assistance (OR = 1.05; 95% CI: 1.01, 1.09). Finally, deaths during heat waves were more likely among residents in areas of the city with higher relative daytime summer surface temperature and less likely among residents living in areas with more green space. Conclusion Mortality during heat waves varies widely within a city. Understanding which individuals and neighborhoods are most vulnerable can help guide local preparedness efforts. Citation Madrigano J, Ito K, Johnson S, Kinney PL, Matte T. 2015. A case-only study of vulnerability to heat wave–related mortality in New York City (2000–2011). Environ Health Perspect 123:672–678; http://dx.doi.org/10.1289/ehp.1408178

Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study

Rationale: Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha‐1 antitrypsin deficiency. Transforming growth factor‐&bgr; and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor‐&bgr;, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking. Objectives: To determine whether angiotensin‐converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT. Methods: The Multi‐Ethnic Study of Atherosclerosis researchers recruited participants ages 45‐84 years from the general population from 2000 to 2002. Medication use was assessed by medication inventory. Percent emphysema was defined as the percentage of lung regions less than −950 Hounsfield units on CTs. Mixed‐effects regression models were used to adjust for confounders. Results: Among 4,472 participants, 12% used an ACE inhibitor and 6% used an ARB at baseline. The median percent emphysema was 3.0% at baseline, and the rate of progression was 0.64 percentage points over a median of 9.3 years. Higher doses of ACE or ARB were independently associated with a slower change in percent emphysema (P = 0.03). Over 10 years, in contrast to a predicted mean increase in percent emphysema of 0.66 percentage points in those who did not take ARBs or ACE inhibitors, the predicted mean increase in participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percentage points (P = 0.01). The findings were of greatest magnitude among former smokers (P < 0.001). Indications for ACE inhibitor or ARB drugs (hypertension and diabetes) and other medications for hypertension and diabetes were not associated independently with change in percent emphysema. There was no evidence that ACE inhibitor or ARB dose was associated with decline in lung function. Conclusions: In a large population‐based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers. Randomized clinical trials of ACE and ARB agents are warranted for the prevention and treatment of emphysema.

New York City Panel on Climate Change 2015 ReportChapter 5: Public Health Impacts and Resiliency

Recent experience from Hurricane Sandy and high-temperature episodes has clearly demonstrated that the health of New Yorkers can be compromised by extreme coastal storms and heat events. Health impacts that can result from exposure to extreme weather events include direct loss of life, increases in respiratory and cardiovascular diseases, and compromised mental health. Other related health stressors—such as air pollution, pollen, and vector-borne, water-borne, and food-borne diseases—can also be influenced by weather and climate. Figure 5.1 illustrates the complex pathways linking extreme weather events to adverse health outcomes in New York City. New York City and the surrounding metropolitan region face potential health risks related to two principal climate hazards: (1) increasing temperatures and heat waves, and (2) coastal storms and flooding. The health impacts of these hazards depend in turn on myriad pathways, the most important of which are illustrated in the figure. Figure 5.1 Pathways linking climate hazards to health impacts in New York City. Although New York City is one of the best-prepared and most climate-resilient cities in the world, there remain significant potential vulnerabilities related to climate variability and change. As part of the NPCC2 process, a team of local climate and health specialists was mobilized to assess current vulnerabilities and to identify strategies that could enhance the resilience of New York City to adverse health impacts from climate events. The goal was to highlight some of the important climate-related health challenges that New York City is currently facing or may face in the future due to climate variability and change, based on emerging scientific understanding. As indicated in Figure 5.1, health vulnerabilities can be magnified when critical infrastructure is compromised. Critical infrastructure is a highly complex, heterogeneous, and interdependent mix of facilities, systems, and functions that are vulnerable to a wide variety of threats, including extreme weather events. For example, delivery of electricity to households depends on a multi-faceted electrical grid system that is susceptible to blackouts that can occur during heat waves. These, in turn, can expose people to greater risk of contact with exposed wires or to greater heat stress due to failure of air conditioning. Understanding and predicting the impacts that extreme weather events may have on health in New York City require careful analysis of these interactions. Two recent plans to enhance climate resiliency in New York City have been released. A Stronger, More Resilient New York (City of New York, 2013) was developed in the aftermath of Hurricane Sandy by a task force of representatives from City agencies and consultants. This plan was informed by a detailed analysis of the impacts of Hurricane Sandy on infrastructure and the built environment and by the NPCC’s updated 2013 climate projections for the New York metropolitan region. It includes more than 250 initiatives and actionable recommendations addressing 14 domains of the built environment and infrastructure including the healthcare system and several other domains relevant to protecting public health. In addition, the 2014 New York City Hazard Mitigation Plan (HMP) (City of New York, 2014), developed by the NYC Office of Emergency Management in collaboration with the Department of City Planning, updated the 2009 HMP and assesses risks from multiple hazards that threaten New York City. These include but are not limited to several climate-related hazards such as coastal storms and heat waves, and it lays out comprehensive strategies and plans to address these hazards. Many of the measures recommended by A Stronger, More Resilient New York and the HMP have already been implemented, are in progress, or are planned (City of New York, 2013; 2014). This chapter does not include a detailed review of these plans, which would be beyond the expertise and charge of the contributors. Nonetheless, the recommendations in this chapter do broadly support the plans laid out in A Stronger, More Resilient New York and the 2014 HMP, and these are referenced at several points where they are especially relevant. Here we focus on summarizing and synthesizing the emerging scientific knowledge on climate-related health hazards, knowledge that can inform ongoing preparedness planning. Key terms related to climate variability and change as they are applied in the health sector are defined in Box 5.1. This is followed by sections describing health risks, vulnerabilities, and resilience strategies for coastal storms and extreme heat events. We then briefly discuss the interactions of climate change with air pollution, pollen, vector-borne diseases, and water- and food-borne diseases. We conclude with recommendations for research and resiliency planning. Box 5.1 Definitions of key cross-cutting terms in the health context Adaptation Initiatives and measures to reduce the vulnerability of natural and human systems against actual or expected climate change effects. Various types of adaptation exist, such as anticipatory and reactive, private and public, and autonomous and planned. For health, physiological adaptation is also relevant.

Exposures Resulting in Safety and Health Concerns for Child Laborers in Less Developed Countries

Objectives. Worldwide, over 200 million children are involved in child labor, with another 20 million children subjected to forced labor, leading to acute and chronic exposures resulting in safety and health (S&H) risks, plus removal from formal education and play. This review summarized S&H issues in child labor, including forced or indentured domestic labor as other sectors of child labor. Specifically, we focused on exposures leading to S&H risks. Methods. We used PubMed, Scopus, Science Direct, and Google Scholar. References were in English, published in 1990–2015, and included data focused on exposures and S&H concerns of child labor. Results. Seventy-six journal articles were identified, 67 met criteria, 57 focused on individual countries, and 10 focused on data from multiple countries (comparing 3–83 countries). Major themes of concern were physical exposures including ergonomic hazards, chemical exposure hazards, and missed education. Childhood labor, especially forced, exploitative labor, created a significant burden on child development, welfare, and S&H. Conclusions. More field researche data emphasizing longitudinal quantitative effects of exposures and S&H risks are needed. Findings warranted developing policies and educational interventions with proper monitoring and evaluation data collection, plus multiple governmental, international organization and global economic reform efforts, particularly in lower-income, less developed countries.