Showing papers by "Frederica P. Perera published in 2017"

Pollution from Fossil-Fuel Combustion is the Leading Environmental Threat to Global Pediatric Health and Equity: Solutions Exist

Abstract: Fossil-fuel combustion by-products are the world’s most significant threat to children’s health and future and are major contributors to global inequality and environmental injustice. The emissions include a myriad of toxic air pollutants and carbon dioxide (CO2), which is the most important human-produced climate-altering greenhouse gas. Synergies between air pollution and climate change can magnify the harm to children. Impacts include impairment of cognitive and behavioral development, respiratory illness, and other chronic diseases—all of which may be “seeded“ in utero and affect health and functioning immediately and over the life course. By impairing children’s health, ability to learn, and potential to contribute to society, pollution and climate change cause children to become less resilient and the communities they live in to become less equitable. The developing fetus and young child are disproportionately affected by these exposures because of their immature defense mechanisms and rapid development, especially those in low- and middle-income countries where poverty and lack of resources compound the effects. No country is spared, however: even high-income countries, especially low-income communities and communities of color within them, are experiencing impacts of fossil fuel-related pollution, climate change and resultant widening inequality and environmental injustice. Global pediatric health is at a tipping point, with catastrophic consequences in the absence of bold action. Fortunately, technologies and interventions are at hand to reduce and prevent pollution and climate change, with large economic benefits documented or predicted. All cultures and communities share a concern for the health and well-being of present and future children: this shared value provides a politically powerful lever for action. The purpose of this commentary is to briefly review the data on the health impacts of fossil-fuel pollution, highlighting the neurodevelopmental impacts, and to briefly describe available means to achieve a low-carbon economy, and some examples of interventions that have benefited health and the economy.

Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group.

Abstract: Background:Characterization of the epigenome is a primary interest for children’s environmental health researchers studying the environmental influences on human populations, particularly those stu...

Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children.

Abstract: Both short and long-term exposure to traffic-related air pollutants have been associated with asthma and reduced lung function. We hypothesized that short-term indoor exposure to fine particulate matter <2.5 μm (PM2.5) and vanadium (V) would be associated with altered buccal cell DNA methylation of targeted asthma genes and decreased lung function among urban children in a nested subcohort of African American and Dominican children. Six day integrated levels of air pollutants were measured from children’s homes (age 9–14; n = 163), repeated 6 months later (n = 98). Buccal samples were collected repeatedly during visits. CpG promoter loci of asthma genes (i.e., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A), arginase 2 (ARG2)) were pyrosequenced and lung function was assessed. Exposure to V, but not PM2.5, was associated with lower DNA methylation of IL4 and IFNγ. In exploratory analyses, V levels were associated with lower methylation of the proinflammatory NOS2A-CpG+5099 among asthmatic overweight or obese children but not nonasthmatics. Short-term exposure to PM2.5, but not V, appeared associated with lower lung function (i.e., reduced z-scores for forced expiratory volume in one second (FEV1, FEV1/ forced vital capacity [FEV1/FVC] and forced expiratory flow at 25–75% of FVC [FEF25–75]). Exposure to V was associated with altered DNA methylation of allergic and proinflammatory asthma genes implicated in air pollution related asthma. However, short-term exposure to PM2.5, but not V, appeared associated with decrements in lung function among urban children.

Effect of personal exposure to black carbon on changes in allergic asthma gene methylation measured 5 days later in urban children: importance of allergic sensitization.

Abstract: Asthma gene DNA methylation may underlie the effects of air pollution on airway inflammation However, the temporality and individual susceptibility to environmental epigenetic regulation of asthma has not been fully elucidated Our objective was to determine the timeline of black carbon (BC) exposure, measured by personal sampling, on DNA methylation of allergic asthma genes 5 days later to capture usual weather variations and differences related to changes in behavior and activities We also sought to determine how methylation may vary by seroatopy and cockroach sensitization and by elevated fractional exhaled nitric oxide (FeNO) Personal BC levels were measured during two 24-h periods over a 6-day sampling period in 163 New York City children (age 9–14 years), repeated 6 months later During home visits, buccal cells were collected as noninvasive surrogates for lower airway epithelial cells and FeNO measured as an indicator of airway inflammation CpG promoter loci of allergic asthma genes (eg, interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A)), arginase 2 (ARG2)) were pyrosequenced at the start and end of each sampling period Higher levels of BC were associated with lower methylation of IL4 promoter CpG−48 5 days later The magnitude of association between BC exposure and demethylation of IL4 CpG−48 and NOS2A CpG+5099 measured 5 days later appeared to be greater among seroatopic children, especially those sensitized to cockroach allergens (RR [95% CI] 055 [037–082] and 067 [045–098] for IL4 CpG−48 and NOS2A CpG+5099, respectively), compared to non-sensitized children (RR [95% CI] 087 [065–117] and 095 [069–133] for IL4 CpG−48 and NOS2A CpG+5099, respectively); however, the difference was not statistically different In multivariable linear regression models, lower DNA methylation of IL4 CpG−48 and NOS2A CpG+5099 were associated with increased FeNO Our results suggest that exposure to BC may exert asthma proinflammatory gene demethylation 5 days later that in turn may link to airway inflammation Our results further suggest that seroatopic children, especially those sensitized to cockroach allergens, may be more susceptible to the effect of acute BC exposure on epigenetic changes

Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter.

Abstract: Physical activity is associated with improvement in lung function; however, pollution exposure during physical activity can lead to a transient reduction in lung function. This paradoxical relationship may be linked to altered T regulatory (Treg) cell activity, which increases with exercise and suppresses airway inflammation, but decreases in association with exposure to air pollution. To clarify these relationships, we investigated buccal cell DNA methylation of the forkhead box p3 (FOXP3) gene promoter, a proposed biomarker of Treg activity. We hypothesized that active urban children would have lower FOXP3 promoter methylation, associated with better lung function compared to non-active children. We also hypothesized that this relationship would be attenuated by high exposure to the air pollutant black carbon (BC). We performed a cross-sectional study of 135 children ages 9–14 who live in New York City. Activity was measured across 6 days. BC exposure was assessed by personal monitors worn for two 24-h periods, followed by lung function assessment. Buccal swabs were collected for DNA methylation analysis of three regions (six CpG sites) in the FOXP3 promoter. In multivariable regression models, overall, there was no significant relationship between physical activity and FOXP3 promoter methylation (p > 0.05). However, in stratified analyses, among children with higher BC exposure (≥1200 ng/m3), physical activity was associated with 2.37% lower methylation in promoter 2 (CpGs −77, −65, and −58) (β estimate = −2.37%, p < 0.01) but not among those with lower BC exposure (β estimate = 0.54%, p > 0.05). Differences across strata were statistically significant (p interaction = 0.04). Among all children, after controlling for BC concentration, promoter 2 methylation was associated with reduced FEV1/FVC (β estimate = −0.40%, p < 0.01) and reduced FEF25–75% (β estimate = −1.46%, p < 0.01). Physical activity in urban children appeared associated with lower FOXP3 promoter methylation, a possible indicator of greater Treg function, under conditions of high BC exposure. Reduced FOXP3 promoter methylation was associated with higher lung function. These findings suggest that physical activity may induce immunologic benefits, particularly for urban children with greater risk of impaired lung function due to exposure to higher air pollution. FOXP3 promoter buccal cell methylation may function as a useful biomarker of that benefit.

Environmental Pollutants and Neurodevelopment: Review of Benefits From Closure of a Coal-Burning Power Plant in Tongliang, China.

Abstract: Background. Understanding preventable causes of neurodevelopmental disorders is a public health priority. Polycyclic aromatic hydrocarbons (PAH) from combustion of fossil fuel, lead, and mercury are among known neurodevelopmental toxicants. Method. For the first time, we comprehensively review the findings from a study by the Columbia Center for Children's Environmental Health and Chinese partners that followed 2 groups of mother-child pairs, one from 2002 and another from 2005, in Tongliang County, China. Pregnant mothers in the 2 cohorts experienced different exposure to PAH because a local coal-burning power plant was shut down in 2004. Investigators assessed change in prenatal PAH exposure, measured using a biomarker (benzo[a]pyrene [BaP]-DNA adducts in cord blood). Developmental quotients were measured using the Gesell Developmental Scales at age 2 and IQ was assessed using the Wechsler Intelligence Scale for Children at age 5. Biologic markers of preclinical response were measured in cord blood: methylation status of long interspersed nuclear elements (LINE1), an indicator of genomic stability, and brain-derived neurotrophic factor (BDNF), a neuronal growth promoter. Analyses accounted for co-exposure to lead and mercury. Results. BaP-DNA adducts were significantly inversely associated with Gesell Developmental Scales scores in the first cohort but not in the second cohort; and levels of BDNF and LINE1 methylation were higher in the second cohort. Conclusion. In this study, reduced exposure to PAH was associated with beneficial effects on neurodevelopment as well as molecular changes related to improved brain development and health. These benefits should encourage further efforts to limit exposure to these toxic pollutants.