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Acute respiratory effects of low-level ozone exposure are not well defined in older adults.MOSES (The Multicenter Ozone Study in Older Subjects), although primarily focused on acute cardiovascular effects, provided an opportunity to assess respiratory responses to low concentrations of ozone in older healthy adults.We performed a randomized crossover, controlled exposure study of 87 healthy adults (59.9 ± 4.5 yr old; 60% female) to 0, 70, and 120 ppb ozone for 3 hours with intermittent exercise. Outcome measures included spirometry, sputum markers of airway inflammation, and plasma club cell protein-16 (CC16), a marker of airway epithelial injury. The effects of ozone exposure on these outcomes were evaluated with mixed-effect linear models. A P value less than 0.01 was chosen a priori to define statistical significance.The mean (95% confidence interval) FEVExposure to ozone at near ambient levels induced lung function effects, airway injury, and airway inflammation in older healthy adults. Clinical trial registered with www.clinicaltrials.gov (NCT01487005).

In 2001, the US Environmental Protection Agency (EPA) adopted stringent new standards for on-highway heavy heavy-duty diesel engine (HHDDE) emissions of particulate matter (PM) and oxides of nitrogen (NOx) that were to become effective during the 2007–2010 time period. The Advanced Collaborative Emissions Study (ACES) was a cooperative, multiparty effort to characterize the emissions (in Phases 1 and 2) and assess the possible health impacts (in Phase 3) of the new, advanced HHDDE technologies, after introducing them to the market. Phase 1 demonstrated that the regulated emissions from four 2007-compliant engines tested were all below the 2007 standards. Both regulated and unregulated emissions were substantially reduced relative to pre-2007 technology engines, except for nitrogen dioxide (NO2) emissions that were higher compared to 2004 technology engines due to the use of diesel oxidation catalyst (DOC) and catalyzed diesel particulate filter (DPF) exhaust aftertreatment technologies. Phase 2 showed another large step in emissions reductions for 2010-compliant diesel engines. The three 2010-compliant engines tested had substantially lower regulated emissions of NOx, CO, NMHC, and PM relative to the emission standards and also relative to the 2007-compliant engines. NOx reductions were achieved using urea-based selective catalytic reduction (SCR) and an ammonia oxidation catalyst (AMOX). A wide spectrum of particle and gas phase unregulated emissions species, including NO2, were also reduced relative to 2007-compliant engines and older engines. Phase 3 consisted of an inhalation bioassay in which rats were exposed for their lifetime to the diluted exhaust from one of the 2007-compliant engines tested in Phase 1. Three exhaust dilutions were selected based on the nitrogen dioxide (NO2) concentrations to achieve three exposure levels: 4.2 ppm (high-DE exposure), 0.8 ppm (mid-DE exposure), and 0.1 ppm (low-DE exposure) NO2. The control exposure consisted of filtered air. NO2 was chosen because the particle concentrations in the exhaust were too low to set the dilution levels. Exposures were conducted 16 h/day, 5 days/week. Rats were evaluated histopathologically and for respiratory function, a large number of noncancer endpoints, and genotoxicity, at interim time points up to the final sacrifice at 28 months (males) and 30 months (females). Histopathological analyses found that exposure to exhaust from a 2007-compliant engine produced no tumors or precancerous effects in lungs and no increase in tumor incidence outside the lung, but induced mild epithelial hyperplasia in the central acinus region of the lung, interstitial fibrosis, and bronchiolization at the high exposure level. The lung histologic changes were consistent with previous findings in rats after long-term exposure to NO2—a major component of the chamber exposure atmosphere, which is substantially reduced in 2010-compliant engines. The majority of the biological endpoints were unchanged with exposure and little inflammation was observed. In summary, the ACES study shows that emissions from 2007- and 2010-compliant HHDDE have been reduced dramatically and that exhaust from a 2007-compliant engine produced no tumors or precancerous effects in rats exposed over their lifetime.

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p

Background To date, there have been relatively few studies of acute cardiovascular responses to controlled ozone inhalation, although a number of observational studies have reported significant positive associations between both ambient ozone levels and acute cardiovascular events and long-term ozone exposure and cardiovascular mortality. Objectives We hypothesized that short-term controlled exposure to low levels of ozone in filtered air would induce autonomic imbalance, repolarization abnormalities, arrhythmia, and vascular dysfunction. Methods This randomized crossover study of 87 healthy volunteers 55–70 years of age was conducted at three sites using a common protocol, from June 2012 to April 2015. Subjects were exposed for 3 h in random order to 0 ppb (filtered air), 70 ppb ozone, and 120 ppb ozone, alternating 15 min of moderate exercise with 15 min of rest. A suite of cardiovascular endpoints was measured the day before, the day of, and up to 22 h after each exposure. Mixed effect linear and logit models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. Site and time were included in the models. Results We found no significant effects of ozone exposure on any of the primary or secondary measures of autonomic function, repolarization, ST segment change, arrhythmia, or vascular function (systolic blood pressure and flow-mediated dilation). Conclusions In this multicenter study of older healthy women and men, there was no convincing evidence for acute effects of 3-h, relatively low-level ozone exposures on cardiovascular function. However, we cannot exclude the possibility of effects with higher ozone concentrations, more prolonged exposure, or in subjects with underlying cardiovascular disease. Further, we cannot exclude the possibility that exposure to ambient ozone and other pollutants in the days before the experimental exposures obscured or blunted cardiovascular biomarker response to the controlled ozone exposures.

“Air Pollution and Health: Bridging the Gap from Sources to Health Outcomes,” an international specialty conference sponsored by the American Association for Aerosol Research, was held to address key uncertainties in our understanding of adverse health effects related to air pollution and to integrate and disseminate results from recent scientific studies that cut across a range of air pollution-related disciplines. The Conference addressed the science of air pollution and health within a multipollutant framework (herein “multipollutant” refers to gases and particulate matter mass, components, and physical properties), focusing on five key science areas: sources, atmospheric sciences, exposure, dose, and health effects. Eight key policy-relevant science questions integrated across various parts of the five science areas and a ninth question regarding findings that provide policy-relevant insights served as the framework for the meeting. Results synthesized from this Conference provide new evidence, reaffirm past findings, and offer guidance for future research efforts that will continue to incrementally advance the science required for reducing uncertainties in linking sources, air pollutants, human exposure, and health effects. This paper summarizes the Conference findings organized around the science questions. A number of key points emerged from the Conference findings. First, there is a need for greater focus on multipollutant science and management approaches that include more direct studies of the mixture of pollutants from sources with an emphasis on health studies at ambient concentrations. Further, a number of research groups reaffirmed a need for better understanding of biological mechanisms and apparent associations of various health effects with components of particulate matter (PM), such as elemental carbon, certain organic species, ultrafine particles, and certain trace elements such as Ni, V, and Fe(II), as well as some gaseous pollutants. Although much debate continues in this area, generation of reactive oxygen species induced by these and other species present in air pollution and the resulting oxidative stress and inflammation were reiterated as key pathways leading to respiratory and cardiovascular outcomes. The Conference also underscored significant advances in understanding the susceptibility of populations, including the role of genetics and epigenetics and the influence of socioeconomic and other confounding factors and their synergistic interactions with air pollutants. Participants also pointed out that short- and long-term intervention episodes that reduce pollution from sources and improve air quality continue to indicate that when pollution decreases so do reported adverse health effects. In the limited number of cases where specific sources or PM2.5 species were included in investigations, specific species are often associated with the decrease in effects. Other recent advances for improved exposure estimates for epidemiological studies included using new technologies such as microsensors combined with cell phone and integrated into real-time communications, hybrid air quality modeling such as combined receptor- and emission-based models, and surface observations used with remote sensing such as satellite data.

The Advanced Collaborative Emissions Study was designed to determine whether new technology heavy-duty diesel engines (NTDE) that are compliant with 2007 and 2010 EPA emissions standards for PM and...

The objective of the Advanced Collaborative Emissions Study (ACES) was to determine before widespread commercial deployment whether or not the new, energy-efficient, heavy duty diesel engines (2007 and 2010 EPA Emissions Standards Compliant) may generate anticipated toxic emissions that could adversely affect the environment and human health. ACES was planned to take place in three phases. In Phase 1, extensive emissions characterization of four production-intent prototype engine and control systems designed to meet 2007 standards for nitrogen oxides (NOx) and particulate matter (PM) was conducted at an existing emissions characterization facility: Southwest Research Institute (SwRI). One of the tested engines was selected (at random, after careful comparison of results) for health testing in Phase 3. In Phase 2, extensive emission characterization of three production-intent prototype engine and control systems meeting the 2010 standards (including more advanced NOx controls to meet the more stringent 2010 NOx standards) was conducted at the same test facility. In Phase 3, one engine/aftertreatment system selected from Phase 1 was further characterized during health effects studies (at an existing inhalation toxicology laboratory: Lovelace Respiratory Research Institute, [LRRI]) to form the basis of the ACES safety assessment. The Department of Energy (DOE) award provided funding for emissionsmore » characterization in Phases 1 and 2 as well as exposure characterization in Phase 3. The main health analyses in Phase 3 were funded separately and are not reported here.« less

The use of oxygenated fuels is anticipated to increase over the next decades. This paper reviews the toxicological and exposure information for methyl tertiary-butyl ether (MTBE), a fuel additive, and methanol, a replacement fuel, and discusses the possible health consequences of exposure of the general public to these compounds. For MTBE, the health effects information available is derived almost exclusively from rodent studies, and the exposure data are limited to a few measurements at some service stations. Based on these data, it appears unlikely that the normal population is at high risk of exposure to MTBE vapor. However, in the absence of health and pharmacokinetic data in humans or in nonhuman primates, this conclusion is not strongly supported. Similarly, there are a number of uncertainties to take into consideration in estimating human risk from the use of methanol as a fuel. Although methanol may be toxic to humans at concentrations that overwhelm certain enzymes involved in methanol metabolism, the data available provide little evidence to indicate that exposure to methanol vapors from the use of methanol as a motor vehicle fuel will result in adverse health effects. The uncertainties in this conclusion are based on the lack of information on dose-response relationship at reasonable, projected exposure levels and of studies examining end points of concern in sensitive species. In developing a quantitative risk assessment, more needs to be known about health effects in primates or humans and the range of exposure expected for the general public for both compounds.

A workshop that brought together representatives of most of the laboratories that have conducted animal and/or human inhalation exposure studies with concentrated ambient air particles (CAPs) was convened by the Health Effects Institute in Boston on May 5, 2004. Participants agreed that CAPs researchers need to make serious efforts to harmonize their experimental and analytical protocols to permit the sharing of lessons learned, questions raised, and opportunities for more definitive studies. Standardized outcome measures based on spirometry and response markers in lung bronchoalveolar lavage (BAL) cells and fluids exist, including the appropriate times after exposure to collect samples and measurements. However, for the emerging focus on cardiac system responses, there are many different electrocardiographic (ECG) endpoints being examined, and little standardization on markers that are most informative about adverse effects; on when the measurements need to be made; and on how to make comparable measurements. The workshop focused on two aspects of dealing with these complexities: sorting out influential particulate matter (PM) components responsible for observed effects, and searching for time-varying responses in continuous outcome data. The need for more complete analyses of PM samples from the CAPs studies was also emphasized, as was obtaining a consistent set of parameters characterizing exposure atmospheres and the ambient PM from which the CAPs are sampled. CAPs studies have already had a significant impact within the air pollution health effects community, especially in regard to cardiovascular system effects, and a follow-up meeting with a greater focus on means to harmonize data collection and analysis is needed.