Evaluating reduced-form modeling tools for simulating ozone and PM2.5 monetized health impacts.

Reduced-form modeling approaches are an increasingly popular way to rapidly estimate air quality and human health impacts related to changes in air pollutant emissions. These approaches reduce computation time by making simplifying assumptions about pollutant source characteristics, transport and chemistry. Two reduced form tools used by the Environmental Protection Agency in recent assessments are source apportionment-based benefit per ton (SA BPT) and source apportionment-based air quality surfaces (SABAQS). In this work, we apply these two reduced form tools to predict changes in ambient summer-season ozone, ambient annual PM2.5 component species and monetized health benefits for multiple sector-specific emission control scenarios: on-road mobile, electricity generating units (EGUs), cement kilns, petroleum refineries, and pulp and paper facilities. We then compare results against photochemical grid and standard health model-based estimates. We additionally compare monetized PM2.5 health benefits to values derived from three reduced form tools available in the literature: the Intervention Model for Air Pollution (InMAP), Air Pollution Emission Experiments and Policy Analysis (APEEP) version 2 (AP2) and Estimating Air pollution Social Impact Using Regression (EASIUR). Ozone and PM2.5 changes derived from SABAQS for EGU scenarios were well-correlated with values obtained from photochemical modeling simulations with spatial correlation coefficients between 0.64 and 0.89 for ozone and between 0.75 and 0.94 for PM2.5. SABAQS ambient ozone and PM2.5 bias when compared to photochemical modeling predictions varied by emissions scenario: SABAQS PM2.5 changes were overpredicted by up to 46% in one scenario and underpredicted by up to 19% in another scenario; SABAQS seasonal ozone changes were overpredicted by 34% to 83%. All tools predicted total PM2.5 benefits within a factor of 2 of the full-form predictions consistent with intercomparisons of reduced form tools available in the literature. As reduced form tools evolve, it is important to continue periodic comparison with comprehensive models to identify systematic biases in estimating air pollution impacts and resulting monetized health benefits.

PM2.5-Attributable Mortality Burden Variability in the Continental U.S.

Epidemiologic studies have consistently observed associations between fine particulate matter (PM2.5) exposure and premature mortality. These studies use air quality concentration information from a combination of sources to estimate pollutant exposures and then assess how mortality varies as a result of differing exposures. Health impact assessments then typically use a single log-linear hazard ratio (HR) per health outcome to estimate counts of avoided human health effects resulting from air quality improvements. This paper estimates the total PM2.5-attributable premature mortality burden using a variety of methods for estimating exposures and quantifying PM2.5-attributable deaths in 2011 and 2028. We use: 1) several exposure models that apply a wide range of methods, and 2) a variety of HRs from the epidemiologic literature that relate long-term PM2.5 exposures to mortality among the U.S. population. We then further evaluate the variability of aggregated national premature mortality estimates to stratification by race and/or ethnicity or exposure level (e.g., below the current annual PM2.5 National Ambient Air Quality Standards). We find that unstratified annual adult mortality burden incidence estimates vary more (e.g., ~3-fold) by HR than by exposure model (e.g., <10%). In addition, future mortality burden estimates stratified by race/ethnicity are larger than the unstratified estimates of the entire population, and studies that stratify PM2.5-attributable mortality HRs by an exposure concentration threshold led to substantially higher estimates. These results are intended to provide transparency regarding the sensitivity of mortality estimates to upstream input choices.

Modeling future asthma attributable to fine particulate matter (PM2.5) in a changing climate: a health impact assessment.

Exposure to fine particulate matter (PM2.5) is associated with asthma development as well as asthma exacerbation in children. PM2.5 can be directly emitted or can form in the atmosphere from pollutant precursors. PM2.5 emitted and formed in the atmosphere is influenced by meteorology; future changes in climate may alter the concentration and distribution of PM2.5. Our aim is to estimate the future burden of climate change and PM2.5 on new and exacerbated cases of childhood asthma. Projected concentrations of PM2.5 are based on the Geophysical Fluid Dynamics Laboratory Coupled Model version 3 climate model, the Representative Concentration Pathway 8.5 greenhouse gas scenario, and two air pollution emissions datasets: a 2011 emissions dataset and a 2040 emissions dataset that reflects substantial reductions in emissions of PM2.5 as compared to the 2011 inventory. We estimate additional PM2.5-attributable asthma as well as PM2.5-attributable albuterol inhaler use for four future years (2030, 2050, 2075, and 2095) relative to the year 2000. Exacerbations, regardless of the trigger, are counted as attributable to PM2.5 if the incident disease is attributable to PM2.5. We project 38 thousand (95% CI 36, 39 thousand) additional PM2.5-attributable incident childhood asthma cases and 29 million (95% CI 27, 31 million) additional PM2.5-attributable albuterol inhaler uses per year in 2030, increasing to 200 thousand (95% CI 190, 210 thousand) additional incident cases and 160 million (95% CI 150, 160 million) inhaler uses per year by 2095 relative to 2000 under the 2011 emissions dataset. These additional PM2.5-attributable incident asthma cases and albuterol inhaler use would cost billions of additional U.S. dollars per year by the late century. These outcomes could be mitigated by reducing air pollution emissions.

Assessing Human Health PM2.5 and Ozone Impacts from U.S. Oil and Natural Gas Sector Emissions in 2025.

Incomplete information regarding emissions from oil and natural gas production has historically made it challenging to characterize the air quality or air pollution-related health impacts for this sector in the United States. Using an emissions inventory for the oil and natural gas sector that reflects information regarding the level and distribution of PM2.5 and ozone precursor emissions, we simulate annual mean PM2.5 and summer season average daily 8 h maximum ozone concentrations with the Comprehensive Air-Quality Model with extensions (CAMx). We quantify the incidence and economic value of PM2.5 and ozone health related effects using the environmental Benefits Mapping and Analysis Program (BenMAP). We find that ambient concentrations of PM2.5 and ozone, and associated health impacts, are highest in a handful of states including Colorado, Pennsylvania, Texas and West Virginia. On a per-ton basis, the benefits of reducing PM2.5 precursor emissions from this sector vary by pollutant species, and range from between $6,300 and $320,000, while the value of reducing ozone precursors ranges from $500 to $8,200 in the year 2025 (2015$).

The reduction of summer sulfate and switch from summertime to wintertime PM2.5 concentration maxima in the United States.

Exposure to particulate matter air pollution with a nominal mean aerodynamic diameter less than or equal to 2.5 µm (PM2.5) has been associated with health effects including cardiovascular disease and death. Here, we add to the understanding of urban and rural PM2.5 concentrations over large spatial and temporal scales in recent years. We used high-quality, publicly-available air quality monitoring data to evaluate PM2.5 concentration patterns and changes during the years 2000-2015. Compiling and averaging measurements collected across the U.S. revealed that PM2.5 concentrations from urban sites experienced seasonal maxima in both winter and summer. Within each year from 2000 to 2008, the maxima of urban summer peaks were greater than winter peaks. However, from 2012 to 2015, the maxima of urban summertime PM2.5 peaks were smaller than the urban wintertime PM2.5 maxima, due to a decrease in the magnitude of summertime maxima with no corresponding decrease in the magnitude of winter maxima. PM2.5 measurements at rural sites displayed summer peaks with magnitudes relatively similar to those of urban sites, and negligible to no winter peaks through the time period analyzed. Seasonal variations of urban and rural PM2.5 sulfate, PM2.5 nitrate, and PM2.5 organic carbon (OC) were also assessed. Summer peaks in PM2.5 sulfate decreased dramatically between 2000 and 2015, whereas seasonal PM2.5 OC and winter PM2.5 nitrate concentration maxima remained fairly consistent. These findings demonstrate that PM2.5 concentrations, especially those occurring in the summertime, have declined in the U.S. from 2000 to 2015. In addition, reduction strategies targeting sulfate have been successful and the decrease in PM2.5 sulfate contributed to the decline in total PM2.5.

The heart as an extravascular target of endothelin-1 in particulate matter-induced cardiac dysfunction.

Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease have been explored, although linkage with specific factors or genes remains limited. These hypotheses may or may not also lead to particulate matter-induced cardiac dysfunction. Evidence pointing to autocrine/paracrine signaling systems as modulators of cardiac dysfunction has increased interest in the emerging role of endothelins as mediators of cardiac function following particulate matter exposure. Endothelin-1, a well-described small peptide expressed in the pulmonary and cardiovascular systems, is best known for its ability to constrict blood vessels, although it can also induce extravascular effects. Research on the role of endothelins in the context of air pollution has largely focused on vascular effects, with limited investigation of responses resulting from the direct effects of endothelins on cardiac tissue. This represents a significant knowledge gap in air pollution health effects research, given the abundance of endothelin receptors found on cardiac tissue and the ability of endothelin-1 to modulate cardiac contractility, heart rate, and rhythm. The plausibility of endothelin-1 as a mediator of particulate matter-induced cardiac dysfunction is further supported by the therapeutic utility of certain endothelin receptor antagonists. The present review examines the possibility that endothelin-1 release caused by exposure to PM directly modulates extravascular effects on the heart, deleteriously altering cardiac function.

Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element.

Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRß antigen receptor locus (Tcrb). Association between distal Vß gene segments and the highly expressed DßJß clusters, termed the recombination center (RC), is independent of enhancer function and recruitment of V(D)J recombinase. Instead, we find that tissue-specific folding of Tcrb relies on two distinct architectural elements located upstream of the RC. The first, a CTCF-containing element, directly tethers distal portions of the Vß array to the RC. The second element is a chromatin barrier that protects the tether from hyperactive RC chromatin. When the second element is removed, active RC chromatin spreads upstream, forcing the tether to serve as a new barrier. Acquisition of barrier function by the CTCF element disrupts contacts between distal Vß gene segments and significantly alters Tcrb repertoires. Our findings reveal a separation of function for RC-flanking regions, in which anchors for long-range recombination must be cordoned off from hyperactive RC landscapes by chromatin barriers.

Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2.

Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that T-cell receptor ß (Tcrb) alleles frequently and stochastically associate with the nuclear lamina and pericentromeric heterochromatin in CD4(-)CD8(-) thymocytes. Moreover, rearranged alleles were underrepresented at these locations. Here we used 3D immunofluorescence in situ hybridization to identify recently rearranged Tcrb alleles based on the accumulation of the DNA-repair protein 53BP1. We found that Tcrb alleles recombine asynchronously in double-negative thymocytes and that V(D)J recombination is suppressed on peripheral as compared with central Tcrb alleles. Moreover, the recombination events that did take place at the nuclear periphery preferentially occurred on Tcrb alleles that were partially dissociated from the nuclear lamina. To understand better the mechanism by which V(D)J recombination is suppressed at the nuclear periphery, we evaluated the subnuclear distribution of recombination-activating gene 2 (RAG2) protein. We found that RAG2 abundance was reduced at the nuclear periphery. Moreover, RAG2 was distributed differently from RNA polymerase II and histone H3K4 trimethylation. Our data suggest that the nuclear periphery suppresses V(D)J recombination, at least in part, by segregating Tcrb alleles from RAG proteins.