Browsing by Subject "Ozone"

In order to meet disinfection guidelines, wastewater utilities must achieve a high level of treatment before discharging treated water for irrigation or industrial use. However, public pressure to reduce disinfection by-products and pharmaceutically-active compounds, recently-promulgated regulations on chlorine-resistant microorganisms such as Cryptosporidium parvum, and growth in population and water demand have driven an interest in alternatives to chlorination. The WateReuse Foundation has funded WRF 02-009 (Innovative Treatment Technologies for Reclaimed Water), which is a survey of current and emerging reuse water treatment technologies. The goal of the project is to evaluate treatment technologies can provide adequate recycled water effluent without the cost of reverse osmosis (RO) or the disinfection by-products (DBPs) formed during chlorination.

The inactivation of indigenous microorganisms (total and fecal coliform bacteria, and total aerobic spores) and spiked surrogate, respiratory, and enteric viruses (MS-2 bacteriophage, adenovirus type 4, reovirus type 3, and coxsackievirus type B5) and chemical degradation by wastewater treatment technologies was evaluated on the bench-scale. These include: low- and medium-pressure UV, LPUV/H₂O₂, ozonation, O₃/H₂O₂, peracetic acid (PAA), LPUV/PAA, chlorination, chloramination, and ultrafiltration. The applicability of the candidate disinfection methods, especially emerging and comparatively untested methods such as PAA and advanced oxidation processes (AOPs), was studied through comparison of their performance and the important water matrix parameters (e.g., alkalinity, BOD, TSS, etc.).

Of the chemical disinfectants, molecular ozone and free chlorine were the most effective, with substantial coliform and virus kill at low doses. Combined chlorine in the form of monochloramine had a reduced disinfectant capacity than free chlorine, and peracetic acid (PAA) performed equally as well as free chlorine with respect to coliform bacteria in some instances but had little to no impact on spiked MS2 bacteriophage. None of the aforementioned disinfectants had an appreciable impact on indigenous aerobic spore-forming bacteria due to their physiology. UV and O₃ rapidly killed human enteric and respiratory viruses, but a consistent benefit by AOPs over their base technologies was not observed for any of their base technologies.

Low and medium-pressure UV inactivated free-floating indigenous coliform bacteria almost immediately, while slower inactivation rates at higher UV fluences illustrated the "tailing" behavior observed when bacteria are embedded in or shielded by particulate matter. Log-linear inactivation of spiked viruses and indigenous aerobic spores by UV was consistent across the utility waters. The UV-based advanced oxidation processes (UV/H₂O₂ and UV/PAA) destroyed spiked organic compounds at much higher rates than direct UV photolysis, while O₃, with or without H₂O₂ , oxidized spiked compounds and reduced estrogenicity (EEQ) at low doses. Recalcitrant chlorinated hydrocarbons such as TCEP were only moderately removed by the tested AOPs, but low doses of O₃ (3 ppm residual O₃) reduced estrogenic activity by 99%. Like other disinfection processes, AOP performance is dependant on pretreatment, especially concerning particulates.

In many spatio-temporal applications a vector of covariates is measured alongside a spatio-temporal response. In such cases, the purpose of the statistical model is to quantify the change, in expectation or otherwise, in the response due to a change in the predictors while adequately accounting for the spatio-temporal structure of the response, the predictors, or both. The most common approach for building such a model is to confine the relationship between the response and the predictors to a single spatio-temporal coordinate. For spatio-temporal problems, however, the relationship between the response and predictors may not be so confined. For example, spatial models are often used to quantify the effect of pollution exposure on mortality. Yet, an unknown lag exists between time of exposure to pollutants and mortality. Furthermore, due to mobility and atmospheric movement, a spatial lag between pollution concentration and mortality may also exist (e.g. subjects may live in the suburbs where pollution levels are low but work in the city where pollution levels are high).

The contribution of this thesis is to propose a hierarchical modeling framework which captures complex spatio-temporal relationships between responses and covariates. Specifically, the models proposed here use kernels to capture spatial and/or temporal lagged effects. Several forms of kernels are proposed with varying degrees of complexity. In each case, however, the kernels are assumed to be parametric with parameters that are easily interpretable and estimable from the data. Full distributional results are given for the Gaussian setting along with consequences of model misspecification. The methods are shown to be effective in understanding the complex relationship between responses and covariates through various simulated examples and analyses of physical data sets.

In the first chapter of this dissertation, I outline a hedonic equilibrium model that explicitly controls for moving costs and forward-looking behavior. Hedonic equilibrium models allow researchers to recover willingness to pay for spatially delineated amenities by using the notion that individuals "vote with their feet." However, the hedonic literature and, more recently, the estimable Tiebout sorting model literature, has largely ignored both the costs associated with migration (financial and psychological), as well as the forward-looking behavior that individuals exercise in making location decisions. Each of these omissions could lead to biased estimates of willingness to pay. Building upon dynamic migration models from the labor literature, I estimate a fully dynamic model of individual migration at the national level. By employing a two-step estimation routine, I avoid the computational burden associated with the full recursive solution and can then include a richly-specified, realistic state space. With this model, I am able to perform non-market valuation exercises and learn about the spatial determinants of labor market outcomes in a dynamic setting. Including dynamics has a significant positive impact on the estimates of willingness to pay for air quality. In addition, I find that location-specific amenity values can explain important trends in observed migration patterns in the United States.

The second chapter of this dissertation describes a model which estimates willingness to pay for air quality using property value hedonics techniques. Since Rosen's seminal 1974 paper, property value hedonics has become commonplace in the non-market valuation of environmental amenities, despite a number of well-known methodological problems. In particular, recovery of the marginal willingness to pay function suffers from important endogeneity biases that are difficult to correct with instrumental variables procedures [Epple (1987)]. Bajari and Benkard (2005) propose a "preference inversion" procedure for recovering heterogeneous measures of marginal willingness to pay that avoids these problems. However, using cross-sectional data, their approach imposes unrealistic constraints on the elasticity of marginal willingness to pay. Following Bajari and Benkard's suggestion, I show how data describing repeat purchase decisions by individual home buyers can be used to relax these constraints. Using data on ozone pollution in the Bay Area of California, I find that endogeneity bias and flexibility in the shape of the marginal willingness to pay function are both important.

Finally, in the third chapter of this dissertation, I combine the insights of the Bajari-Benkard inversion approach employed in second chapter with more standard estimation techniques (i.e., Rosen (1974)) to arrive at a new hedonic methodology that allows for flexible and heterogeneous preferences while avoiding the endogeneity problems that plague the traditional Rosen two-stage model. Implementing this estimator using the Bay Area ozone data, I again find evidence of considerable heterogeneity and of endogeneity bias. In particular, I find that a one unit deterioration in air quality (measured in days in which ozone levels exceed the state standards) raises marginal willingness to pay by $145.18 per year. The canonical two-stage Rosen model finds, counter-intuitively, that this same change would reduce marginal willingness to pay by $94.24.

Lung inflammation, caused by acute exposure to ozone (O3)– one of the six criteria air pollutants – is a significant source of morbidity in susceptible individuals. The adverse effects of ozone (O3) on respiratory health and its significant impact on global public health are well-established, but the cellular mechanisms that drive these effects remain poorly understood. This study explores mechanisms that regulate resolution of O3-induced lung inflammation, specifically focused on the function of alveolar macrophages. Alveolar macrophages (AMØs) are central regulators of lung immune responses including both the initiation and resolution of inflammation. They regulate inflammation via functions such as production of cytokines, phagocytosis, and efferocytosis. While prior O3 exposure studies have highlighted that exposure leads to an increase in AMØs, the specific role of AMØs in promoting resolution of O3-induced lung inflammation remains unclear.One reason that it is challenging to define the role of AMØs following acute O3 exposure is that within the lung, macrophages can have different origins (ontogeny). This has directed a series of studies focused on determining if differences in AMØ functions are due to their distinct ontogeny. While it has been observed that AMØ derived from circulating monocytes (i.e. monocyte-derived AMØs) play a critical role in regulating chronic/severe injury, the ontogeny of AMØs (i.e. tissue-resident versus monocyte-derived) following acute O3 exposure has been undefined. Using mouse models (lineage labeled, genetic knockouts, and wildtype), we traced the origin of AMØs and found them to be predominantly tissue-resident AMØs following acute O3 exposure, which was then confirmed using data from O3-exposed human volunteers. Depletion of these tissue-resident AMØs resulted in a persistence of neutrophils in the alveolar space after O3 exposure, indicating impaired clearance and persistent inflammation. This impaired clearance was associated with reduced efferocytosis, the clearance of apoptotic cells, a process crucial for resolving inflammation. Mice with a genetic deficiency in MerTK – a key receptor regulating efferocytosis – also resulted in impaired clearance of apoptotic neutrophils following O3 exposure. We thus defined the pivotal role of tissue-resident AMØs in resolving O3-induced inflammation via MerTK-mediated efferocytosis. We then focused on intracellular mechanisms of inflammation resolution that occur within AMØs. We focused on a previously established pathway of inflammation resolution regulation through the metabolism of the amino acid, L-arginine. While L-arginine metabolism by nitric oxide synthase can promote inflammatory responses, L-arginine metabolism by arginase-1 generates metabolites that have the potential to direct inflammation resolution. One such metabolite of L-arginine is spermidine, and it is of interest due to its anti-inflammatory properties observed in many tissues (pulmonary and non-pulmonary) and macrophages. Additionally, prior research suggests that spermidine inhibits N-methyl-d-aspartate (NMDA) receptor activation. We therefore hypothesized that the mechanism by which spermidine leads to resolution of macrophage-derived inflammation is via inhibition of NMDA, and thereby reducing the activation of the pro-inflammatory Nuclear factor kappa B (NF-κB) signaling. Here we expand the understanding of the mechanism for spermidine effect in macrophages via impact on NF-κB signaling via the NMDA receptor. To address this, we initially utilized a mouse model to assess the concentration of L-arginine and its metabolites in BALF following acute O3 exposure. Here, we identified a decrease of L-arginine at 12h post-exposure, with a subsequent increase in spermidine present at 24h post-exposure, a time point critical for resolution of O3-induced lung inflammation. We then conducted a pretreatment exposure in which the mice were treated with spermidine prior to O3 exposure to determine if there was a reduction in inflammation. Mice pretreated with spermidine, when compared to control mice, demonstrated reduced O3-induced lung inflammation. This suggests that spermidine may drive a reduction in pro-inflammatory signaling following acute O3 exposure. We next sought to understand the potential intracellular mechanism driving this response. To test this, we conducted in vitro studies in MH-S cells, AMØ-like immortalized cells. We utilized MH-S cells to define spermidine's effect on pro-inflammatory signaling following Lipopolysaccharide (LPS) exposure. We utilized LPS as a known pro-inflammatory stimulus in AMØ and a canonical activator of NF-κB. Utilizing a rescue model, in which spermidine was given following an initial LPS exposure, we found that spermidine decreased the expression and concentration of NF-κB associated pro-inflammatory cytokines, supporting a role in the resolution of inflammation. Then we pretreated MH-S cells with spermidine and determined that spermidine decreases the activation of NF-κB. We then utilized a known agonist, NMDA, for the NMDA receptor and found that NMDA activates NF-κB. In summary, the research highlights the pivotal role of tissue-resident AMØs and explores the potential of spermidine as a therapeutic agent for resolving environmental-induced lung inflammation.

Ground-level ozone values have been reported to be at unhealthy levels in many populated regions of China. An efficient and effective way for people to combat its harmful effects is seriously needed. However, there are only sparse measurements of ozone being made across China and more measurement sites are needed to understand health relevant concentrations both temporally and spatially. This is due in part to the fact that current monitoring approaches are costly and bulky. Ambient sensors with low cost, small size, and fast response time could potentially fill the current need. Our purpose in this study is to evaluate low cost, portable, and real-time sensors we hope to use in future studies. This study tested the effectiveness of the sensors in monitoring indoor and outdoor air quality, in particular ozone, in Beijing, China.

Seventeen sensors, which were to monitor indoor, outdoor, and personal ozone exposure in 7 homes, were collocated at Peking University (PKU) before and after running in selected residential homes. Pairwise comparisons were conducted using collocated sensor data with data from a standing reference sensor which was maintained by PKU to have best-fit regressions. Based on the best-fit regression when compiling both pre- and post- collocation periods, cleaned sensor data was calibrated and compared with reference data with R2 ranging from 0.63 to 0.97. Overall, the sensors are able to measure O3 within ±17 ppb. Average error of sensors after calibration is about -1 ppb. The geographical conditions and surroundings caused significant differences to the ambient ozone concentrations from sensors located across Beijing. Second, the sensors successfully showed that indoor ozone concentrations were likely to be lower when air filtration was on compared to the concentrations when filters were off. Moreover, the results confirmed higher levels of ozone outdoor concentrations compared to indoor. After calibration, average indoor O3 concentration ranged -2 ppb to 23 ppb, while outdoor O3 concentration was from 19 ppb to 47 ppb. The only personal sensor that worked well measured the average personal exposure as about 33 ppb. The peak of ozone outdoor concentration was usually 100 ppb higher than indoor concentration.

Several factors were considered that could affect the accuracy of the sensors including temperature (degree C), relative humidity (RH%), and concentrations of other chemicals in the ambient environment such as Nitrogen Oxides (NO2, NO). However, the impacts of those factors on the performance of sensors were not significant after calibration with little or no correlation between errors and those factors. Therefore, the calibrations based on the simple linear regressions between the sensors and the reference when collocated were valid on the data during the whole sampling period.

It has been commonly accepted until recently that particulate matter (PM) is responsible for the cardiovascular toxicity of air pollution mixtures, while ozone (O3) mainly adversely affects respiratory health. However, there is increasing evidence that O3, independent of PM, is also associated with cardiovascular hospitalizations and mortality, even at levels below current regulatory standards. The mechanisms underlying these epidemiological associations between O3 and cardiovascular disease remain poorly understood. The goal of this dissertation research is to use human biomarker outcomes in real-world exposure scenarios to elucidate plausible mechanisms by which O3 affects cardiovascular health.

The findings of this dissertation research are primarily based on a single longitudinal cohort study designed to assess biomarker associations with time-activity-adjusted air pollutant exposures and with indoor air purification interventions, specifically different combinations of a high efficiency particulate air (HEPA) filter and a particle-removing and O3-producing electrostatic precipitator (ESP). Eighty-nine healthy participants living on a work campus in Changsha City, China were recruited for this study conducted from December 1st, 2014 - January 31st, 2015. The unique quasi-experimental setting of participants all living and working together on a work campus allowed for better characterization of air pollutant exposure effects due to minimal variation in potential confounders. At baseline, workers had a combination of an ESP and a HEPA in the central air handling units (AHUs) of their work and living spaces. During a five-week intervention period from December 6th, 2014 to January 13th, 2015, subjects were split into two groups, both of which had the ESPs turned off and one of which also had the HEPAs removed, and after this intervention original conditions were restored. Biomarkers indicative of inflammation and oxidative stress, arterial stiffness, myocardial function, blood pressure, thrombotic factors, and spirometry were measured at four sessions, one at baseline, two at two and four weeks into the intervention period, and one two weeks after restoring baseline conditions post-intervention. Indoor and outdoor O3 and PM of less than or equal to 2.5 µm in diameter (PM2.5), along with ambient co-pollutants NO2 and SO2, were monitored throughout the study period and combined with time-activity information and filtration conditions of each residence and office. These data were used to estimate 24-hour and 2-week combined indoor and outdoor average exposure concentrations, in addition to exposures in filtered and unfiltered environments.

To test the hypothesis that air pollutant exposures observed during this study would be associated with biomarker outcomes, associations between each exposure measure and biomarker were analyzed with single- and two-pollutant linear mixed models. The 24-hour mean O3 exposure concentrations during the study ranged from 1.4 to 19.4 ppb, corresponding with daily 8-hour maximum outdoor concentrations ranging from 3.6 to 60.5 ppb, with all but six days during the study period falling below the WHO 8-hour mean O3 guideline of 50 ppb6. Within this range, in models controlling for a second co-pollutant and other potential confounders, a 10 ppb increase in 24-hour O3 was associated with mean percent increases (95% CIs) of 36.3% (29.9%, 43.0%) in the platelet activation marker soluble P-selectin (sCD62P), 2.8% (0.6%, 5.1%) in diastolic blood pressure (DBP), and 18.1% (4.5%, 33.5%) and 31.0% (0.2%, 71.1%) in the pulmonary inflammation markers fractional exhaled nitric oxide (FeNO) and exhaled breath condensate nitrite and nitrate (EBCNN), respectively, as well as a -9.5% (-17.7%, -1.4%) decrease in arterial stiffness marker augmentation index (AI) and a -15.5% (-23.8%, -6.2%) decrease in the systemic oxidative stress marker urinary malondialdehyde (UMDA). A 10 ppb increase in 2-week O3 was associated with increases of 61.1% (37.8%, 88.2%) in sCD62P and 126.2% (12.1%, 356.2%) in EBCNN. In contrast, PM2.5, NO2, and SO2 exposure measures were variably and weakly associated with markers indicating increased arterial stiffness and endothelial cell dysfunction. Only the O3 associations with sCD62P are robust in two-pollutant models and multiple testing p-value correction. These results suggest that O3 exposure enhances cardiovascular disease risk through platelet activation and blood pressure increases at levels lower than those capable of affecting lung function.

To examine if the removal of HEPA filtration and ESP in the indoor air purification systems were associated with changes in biomarker outcomes, Bayesian hierarchical generalized ridge regression (GRR) models accounting for subject-specific intercept random effects were used to assess associations between categorical intervention variables while controlling for cumulative pollutant exposures in unfiltered microenvironments, namely outdoors and places other than the offices and dorms. The GRR models allowed for more stable maximized likelihood estimates when model predictors were highly correlated. When factoring in time-activity patterns, subjects without HEPA filtration had total 24-hour PM2.5 exposures on average 37.9 µg/m3 (88.3%) higher than subjects with HEPA filtration, and the removal of the ESPs resulted in a small average reduction of 2.2 ppb (a 32.8% decrease as compared to the overall mean 24-hour O3 exposure) in each subject’s total 24-hour O3 exposure. Despite this large change in PM2.5 exposure, no biomarkers were associated with HEPA removal in any models, but ESP removal was associated with decreases of -17.1% (-23.1%, -11.3%) in sCD62P, -3.6% (-5.5%, -1.4%) in systolic blood pressure (SBP), and -3.3% (-5.9%, -0.7%) in DBP. In addition, though subjects spent an average of 64.5% of their time in filtered locations during each two-week period between sampling visits, cumulative air pollutant exposure in unfiltered environments was associated with increased sCD62P for O3, increased FeNO for PM2.5, and increased EBC MDA and decreased subendocardial viability ratio (SEVR, a marker of myocardial oxygen supply and demand) for SO2. This study suggests that ESP use may result in O3-associated adverse health effects, biomarkers traditionally associated with PM exposure may not show a response weeks into an intervention, and time spent in environments filtered by particulate air filters, though perhaps not ESPs, should be maximized to avoid the health effects of cumulative high exposures in unfiltered locations.

These O3 associations with platelet activation and blood pressure are consistent with related results in some studies but not others, and so I hypothesized that age and sex may influence each individual’s response to O3 and account for some of this variability. I tested this hypothesis by assessing pollutant exposure by age or by sex interaction term estimates in association with biomarker outcomes in the GRR models. This statistical analysis was applied not only to the main study conducted in Changsha, but also to a subsequent study conducted in Shanghai with similar exposure and biomarker measurements that had younger study participants with more balanced sex ratio. In addition, the exposure and biomarker data between these two studies were pooled for an additional analysis checking the results from the individual study findings. In the main Changsha Study, significant age by pollutant exposure interaction terms were observed for the associations between 24-hour and 2-week O3 and sCD62P, 2-week O3 and SBP, and 2-week SO2 and PWV. In addition, the association between PWV and 2-week SO2 was significantly higher in men, and the association between PWV and 24h O3 was significantly higher in women, though the latter interaction term became nonsignificant in a sensitivity analysis assessing the independent interaction effect. No interaction terms were significant in the Shanghai Study analysis. In the pooled analysis, the 24-hour O3 exposure by age interaction term was significant for both sCD62P and SBP. Also, the pooled analysis showed that women had a significantly higher association between 24-hour O3 exposure and PWV as had been seen in the Changsha Study, but as in that case this association was not robust to the sensitivity analyses. These results indicate that older individuals are more susceptible to O3-associated effects on platelet activation and blood pressure, which is supported by literature examining age-associated changes in platelets and vascular tone.

Taken together these results and the findings in previous research examining cardiovascular pathophysiologic mechanisms, a coherent, plausible mechanistic pathway emerges. In this pathway, O3-associated reaction products in the airway lead to the propagation of signals that activate platelets, which in turn enhance blood pressure and induce a procoagulant state. The findings of this dissertation contribute to the mechanistic understanding of how O3 exposure affects cardiovascular health outcomes.