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Respiratory-tract infection, specifically pneumonia, contributes substantially to the increased morbidity and mortality among elderly individuals exposed to airborne particulate matter of < 10 µm diameter (PM[sub 10]). These epidemiological findings suggest that PM[sub 10] may act as an immunosuppressive factor that can undermine normal pulmonary antimicrobial defense mechanisms. To investigate whether, and how, compromised pulmonary immunocompetence might contribute to increased mortality, two sets of laboratory studies were performed. The first examined the effects of a single inhalation exposure to concentrated ambient PM[sub 2.5] (CAPS) from New York City air on pulmonary/systemic immunity and on the susceptibility of exposed aged rats to subsequent infection with Streptococcus pneumoniae. The second set of studies determined whether CAPS exposure, at a concentration approximating or somewhat greater than the promulgated 24-h NAAQS of 65 µg/m³, could exacerbate an ongoing infection. Taken together, results demonstrated that a single exposure of healthy animals to CAPS had little effect on pulmonary immune function or bacterial clearance during subsequent challenge with S. pneumoniae. Alternatively, CAPS exposure of previously infected rats significantly increased bacterial burdens and decreased percentages of lavageable neutrophils and proinflammatory cytokine levels compared to those in infected filtered-air-exposed controls. These studies demonstrate that a single exposure to ambient PM[sub 2.5] compromises a host's ability to handle ongoing pneumococcal infections and support the epidemiological findings of increased pneumonia-related deaths in ambient PM-exposed elderly individuals. [ABSTRACT FROM AUTHOR]

In addition to developing nations relying almost exclusively upon biomass fuels, such as wood for cooking and home heating, North Americans, particularly in Canada and the northwestern and northeastern sections of the United States, have increasingly turned to woodburning as an alternate method for domestic heating because of increasing energy costs. As a result, the number of households using woodburning devices has increased dramatically. This has resulted in an increase in public exposure to indoor and outdoor woodsmoke-associated pollutants, which has prompted widespread concern about the adverse human health consequences that may be associated with prolonged woodsmoke exposure. This mini-review article brings together many of the human and animal studies performed over the last three decades in an attempt to better define the toxicological impact of inhaled woodsmoke on exposed children and adults; particular attention is given to effects upon the immune system. General information regarding occurrence and woodsmoke chemistry is provided so as to set the stage for a better understanding of the toxicological impact. It can be concluded from this review that exposure to woodsmoke, particularly for children, represents a potential health hazard. However, despite its widespread occurrence and apparent human health risks, relatively few studies have focused upon this particular area of research. More laboratory studies aimed at understanding the effects and underlying mechanisms of woodsmoke exposure, particularly on those individuals deemed to be at greatest risk, are badly needed, so that precise human health risks can be defined, appropriate regulatory standards can be set, and accurate decisions can be made concerning the use of current and new woodburning devices. [ABSTRACT FROM AUTHOR]

A major health hazard to coal miners is development of emphysema following long-term exposure to coal dust. One mechanism underlying development of emphysema is the oxidation of critical methionine (Met) residues in antiproteolytic factor, α1-antitrypsin (A1AT) resulting in a protease-antiprotease imbalance in the lung. Several studies have documented an association between the incidence and severity of emphysema among miners and their exposure to crystalline silica (i.e., SiO[sub 2]). However, what remains unclear is the role of other co-inhaled nonemphysematogenic nonoxidant inorganic constituent in disease pathogenesis. We hypothesize that in miners, inhaled trivalent chromium (Cr[sup 3+], the only form of Cr in coal) may potentially affect lung A1AT activity in situ via Cr complexing with Met residues, and thereby exacerbate any SiO[sub 2]-induced imbalance. To ascertain if Cr[sup 3+] could, in fact, affect A1AT activity, in vitro studies were done to assess elastase inhibitory activity following A1AT incubation with soluble Cr[sup 3+]. In addition, to determine if Cr[sup 3+] found in the lungs as detoxification products of inhaled hexavalent Cr (Cr[sup 6+]) could affect A1AT in situ, lavages from the lungs of chromate-exposed rats were also analyzed for elastase inhibitory activity. The in vitro results indicate that Cr[sup 3+] ions clearly inhibited A1AT function, with an IC50 of 1.1 mM being estimated under the experimental conditions used. The in vivo results indicate that long-term inhalation (12 wk or longer) of chromate-bearing atmospheres also gave rise to significant (i.e., 50–70%) inhibition of the antielastase activity of A1AT. Together, these results clearly suggest that the Cr[sup 3+] present in coal dusts could potentially act to inhibit A1AT activity in the lungs of miners and thereby promote the emphysematogenicity of SiO[sub 2] or of other emphysematogens present as coconstituents in these dusts. [ABSTRACT FROM AUTHOR]

The goal of this study was to examine effects from repeated exposure to ozone (O[sub 3]) on immune cells involved in cell-mediated antibacterial responses in the lungs. Rats exposed to 0.1 or 0.3 ppm O[sub 3] for 4 h/day, 5 days/wk, for 1 or 3 wk were analyzed for the ability to clear an intrapulmonary challenge with Listeria monocytogenes or had their lungs processed to obtain pulmonary alveolar macrophages (PAM) and lung-associated lymphocytes for analyses of select cell functions and surface marker expression. The results indicate that repeated inhalation exposure to O[sub 3] affected local cell-mediated immunity (CMI) responses as evidenced by effects on clearance of Listeria. However, this modulation was not consistently dependent on exposure concentration or duration. Short-term repeat exposures had more effect on host resistance than did the more prolonged regimen, with rats exposed to 0.1 ppm O[sub 3] most adversely impacted. Clearance patterns suggest modifications in innate resistance following 1 wk of exposure to 0.1 ppm O[sub 3], but no similar effect following a 3-wk regimen. Exposure to 0.3 ppm O[sub 3] appeared to affect both innate and acquired resistance after a 1-wk regimen, but mainly the former after an additional 2 wk of exposure. We conclude that these two mechanisms of resistance are differentially affected by O[sub 3] and that distinct time- and O[sub 3] concentration-dependent adaptation phenomena evolve for each; that is, in situ adaptation to higher levels of O[sub 3] may occur more readily with acquired than with innate/PAM-dependent resistance. A similar pattern of inconsistent effect on PAM and lung-associated lymphocytes was also evident. For example, while 3-wk exposures had a greater effect on PAM reactive oxygen intermediate ROI production, evidence for a significant effect on antibacterial activity was only notable among PAM from rats exposed for 1 wk. Among lung lymphocytes, while 3-wk exposure to 0.1 ppm O[sub 3] led to a significant increase in CD25 expression, there was no corresponding increase in responsivity to concanavalin A (ConA); only among cells from 1-wk-exposed rats did lymphoproliferative responses increase. Though investigations of altered immune cell cytokine receptor expression/binding activity are ongoing, results herein provide further evidence to support our longstanding hypothesis that some well-documented effects of O[sub 3] exposure on human health are quite likely linked to changes in local immune cell (i.e., PAM and lung-associated lymphocytes) functions, with the latter being related to changes in the capacities of these cells to interact with immunoregulatory cytokines. [ABSTRACT FROM AUTHOR]

Unlabelled: In 2012, the WHO classified diesel emissions as carcinogenic, and its European branch suggested creating a public health standard for airborne black carbon (BC). In 2011, EU researchers found that life expectancy could be extended four to nine times by reducing a unit of BC, vs reducing a unit of PM2.5. Only recently could such determinations be made. Steady improvements in research methodologies now enable such judgments. In this Critical Review, we survey epidemiological and toxicological literature regarding carbonaceous combustion emissions, as research methodologies improved over time. Initially, we focus on studies of BC, diesel, and traffic emissions in the Western countries (where daily urban BC emissions are mainly from diesels). We examine effects of other carbonaceous emissions, e.g., residential burning of biomass and coal without controls, mainly in developing countries. Throughout the 1990s, air pollution epidemiology studies rarely included species not routinely monitored. As additional PM2.5. chemical species, including carbonaceous species, became more widely available after 1999, they were gradually included in epidemiological studies. Pollutant species concentrations which more accurately reflected subject exposure also improved models. Natural "interventions"--reductions in emissions concurrent with fuel changes or increased combustion efficiency; introduction of ventilation in highway tunnels; implementation of electronic toll payment systems--demonstrated health benefits of reducing specific carbon emissions. Toxicology studies provided plausible biological mechanisms by which different PM species, e.g, carbonaceous species, may cause harm, aiding interpretation of epidemiological studies. Our review finds that BC from various sources appears to be causally involved in all-cause, lung cancer and cardiovascular mortality, morbidity, and perhaps adverse birth and nervous system effects. We recommend that the US. EPA rubric for judging possible causality of PM25. mass concentrations, be used to assess which PM2.5. species are most harmful to public health., Implications: Black carbon (BC) and correlated co-emissions appear causally related with all-cause, cardiovascular, and lung cancer mortality, and perhaps with adverse birth outcomes and central nervous system effects. Such findings are recent, since widespread monitoring for BC is also recent. Helpful epidemiological advances (using many health relevant PM2.5 species in models; using better measurements of subject exposure) have also occurred. "Natural intervention" studies also demonstrate harm from partly combusted carbonaceous emissions. Toxicology studies consistently find biological mechanisms explaining how such emissions can cause these adverse outcomes. A consistent mechanism for judging causality for different PM2.5 species is suggested.

Particulate matter (PM) pollution is responsible for hundreds of thousands of deaths worldwide, the majority due to cardiovascular disease (CVD). While many potential pathophysiological mechanisms have been proposed, there is not yet a consensus as to which are most important in causing pollution-related morbidity/mortality. Nor is there consensus regarding which specific types of PM are most likely to affect public health in this regard. One toxicological mechanism linking exposure to airborne PM with CVD outcomes is oxidative stress, a contributor to the development of CVD risk factors including atherosclerosis. Recent work suggests that accelerated shortening of telomeres and, thus, early senescence of cells may be an important pathway by which oxidative stress may accelerate biological aging and the resultant development of age-related morbidity. This pathway may explain a significant proportion of PM-related adverse health outcomes, since shortened telomeres accelerate the progression of many diseases. There is limited but consistent evidence that vehicular emissions produce oxidative stress in humans. Given that oxidative stress is associated with accelerated erosion of telomeres, and that shortened telomeres are linked with acceleration of biological ageing and greater incidence of various age-related pathology, including CVD, it is hypothesized that associations noted between certain pollution types and sources and oxidative stress may reflect a mechanism by which these pollutants result in CVD-related morbidity and mortality, namely accelerated aging via enhanced erosion of telomeres. This paper reviews the literature providing links among oxidative stress, accelerated erosion of telomeres, CVD, and specific sources and types of air pollutants. If certain PM species/sources might be responsible for adverse health outcomes via the proposed mechanism, perhaps the pathway to reducing mortality/morbidity from PM would become clearer. Not only would pollution reduction imperatives be more focused, but interventions which could reduce oxidative stress would become all the more important.

A major public health goal is to determine linkages between specific pollution sources and adverse health outcomes. This paper provides an integrative evaluation of the database examining effects of vehicular emissions, such as black carbon (BC), carbonaceous gasses, and ultrafine PM, on cardiovascular (CV) morbidity and mortality. Less than a decade ago, few epidemiological studies had examined effects of traffic emissions specifically on these health endpoints. In 2002, the first of many studies emerged finding significantly higher risks of CV morbidity and mortality for people living in close proximity to major roadways, vs. those living further away. Abundant epidemiological studies now link exposure to vehicular emissions, characterized in many different ways, with CV health endpoints such as cardiopulmonary and ischemic heart disease and circulatory-disease-associated mortality; incidence of coronary artery disease; acute myocardial infarction; survival after heart failure; emergency CV hospital admissions; and markers of atherosclerosis. We identify numerous in vitro, in vivo, and human panel studies elucidating mechanisms which could explain many of these cardiovascular morbidity and mortality associations. These include: oxidative stress, inflammation, lipoperoxidation and atherosclerosis, change in heart rate variability (HRV), arrhythmias, ST-segment depression, and changes in vascular function (such as brachial arterial caliber and blood pressure). Panel studies with accurate exposure information, examining effects of ambient components of vehicular emissions on susceptible human subjects, appear to confirm these mechanisms. Together, this body of evidence supports biological mechanisms which can explain the various CV epidemiological findings. Based upon these studies, the research base suggests that vehicular emissions are a major environmental cause of cardiovascular mortality and morbidity in the United States. As a means to reduce the public health consequences of such emissions, it may be desirable to promulgate a black carbon (BC) PM(2.5) standard under the National Ambient Air Quality Standards, which would apply to both on and off-road diesels. Two specific critical research needs are identified. One is to continue research on health effects of vehicular emissions, gaseous as well as particulate. The second is to utilize identical or nearly identical research designs in studies using accurate exposure metrics to determine whether other major PM pollutant sources and types may also underlie the specific health effects found in this evaluation for vehicular emissions.

Ambient air particulate matter (PM) originates as either primary particles emitted directly into the atmosphere from a specific source or as secondary particles produced from atmospheric chemical reactions between precursor gases or between these gases and primary particles. PM can derive from both natural and anthropogenic sources, resulting in a complex chemical mix. The "fine" size mode of ambient PM, designated as PM(2.5), is defined as comprising those particles having aerodynamic diameters below 2.5 microm. While the total mass of PM(2.5) has been associated with adverse human health outcomes, the relationship between these and specific chemical components has not been resolved. This article provides a perspective on the current state of the science concerning health effects from a major group of chemical species found within PM(2.5), namely common inorganic constituents. The specific chemical classes discussed herein are secondary inorganic species, namely, sulfate, nitrate, and acidity, and generally crustal-derived species, namely, phosphate, sodium, potassium, calcium, magnesium, silicon, and aluminum. The article discusses evidence for adverse health effects from inorganic PM(2.5) components within the framework of various caveats surrounding both epidemiology and toxicology assessments. The largest database exists for sulfate, but conclusions that attribute sulfate to health outcomes have not been consistent across all epidemiology studies, and there is a lack of coherence with toxicology studies, which show biological responses only at high levels of exposure. Limited epidemiological and toxicological data for nitrate suggests little or no adverse health effects at current levels. Epidemiological studies specifically identifying crustal components of PM(2.5) suggest that they are not likely, by themselves, to produce a significant health risk, and these components do not have unequivocal biological plausibility from toxicological studies for being significant contributors to adverse health outcomes.

Researchers and regulators have often considered preferentially regulating the types of ambient airborne particulate matter (PM) most relevant to human health effects. While few would argue the inherent merits of such a policy, many believe there may not yet be enough information to differentially regulate PM species. New evidence, using increasingly sophisticated methodologies, has become available in the last several years, allowing more accurate assessment of exposure and resultant associations with specific types of PM, or PM derived from different sources. Such new studies may also allow differentiation of effects from different chemical components in the same study against the same health endpoints. This article considers whether this new evidence might be adequate to allow us to "speciate" PM types or sources by severity of health effects. We address this issue with respect to two widespread sources of PM, emissions from motor vehicles and coal-fired power plants. Emissions from less widespread sources, residual oil and steel/coking facilities, are also discussed in order to illustrate how health effects associated with such emissions might instead be associated with more widespread sources when accurate exposure information is unavailable. Based upon evaluation of studies and methodologies which appear to contain the most accurate information on exposure and response to important emissions, including variable local emissions, it is concluded that public health will likely be better protected by reduction of various vehicular emissions than by continued regulation of the total mass of fine PM (PM <2.5 microm, or PM2.5) as if all PM in this mode is equitoxic. However, the knowledge base is incomplete. Important remaining research questions are identified.

Epidemiological studies have provided evidence for an association between exposure to ambient particulate matter and increased mortality and morbidity. However, the exact physicochemical nature of the responsible components is not as yet clear. One major constituent of the ambient aerosol is secondary inorganic particles, which are produced within the atmosphere via chemical reactions and are dominated by sulfates and nitrates. This article reviews the biological effects resulting from exposure to these ambient aerosol constituents. It was developed based upon available data from peer reviewed published papers as well as publicly available reports on controlled animal and human clinical exposure studies. The aim was to provide a toxicological basis for addressing the issue of whether ambient concentrations of these secondary aerosols in two venues, namely the United States and the Netherlands, could be causally related to reported human health effects associated with exposure to ambient particulate matter. Evaluation of the toxicological database suggests that these particles have little biological potency in normal humans or animals, or in the limited compromised animal models studied at environmentally relevant levels. There are, however, some critical caveats in this analysis that must be considered. First, it is important to understand the relationship between animal exposure studies and actual human exposures, in terms of both particle size and inhaled dose. Second, it is necessary to consider the physicochemical characteristics of the chemical species within ambient air compared to the characteristics of those used in controlled studies. Third, there is the issue of relevance of the exposure models used in these studies to those populations that may be affected by exposure to ambient particulates. Finally, the potential for interactions between particulates and ambient gases in the total atmospheric mix must be considered in developing conclusions as to exposure concentrations for the former constituents of polluted air that may be hazardous to public health.

A major health hazard to coal miners is development of emphysema following long-term exposure to coal dust. One mechanism underlying development of emphysema is the oxidation of critical methionine (Met) residues in antiproteolytic factor, alpha1-antitrypsin (A1AT) resulting in a protease-antiprotease imbalance in the lung. Several studies have documented an association between the incidence and severity of emphysema among miners and their exposure to crystalline silica (i.e., SiO(2)). However, what remains unclear is the role of other co-inhaled nonemphysematogenic nonoxidant inorganic constituent in disease pathogenesis. We hypothesize that in miners, inhaled trivalent chromium (Cr(3+), the only form of Cr in coal) may potentially affect lung A1AT activity in situ via Cr complexing with Met residues, and thereby exacerbate any SiO(2)-induced imbalance. To ascertain if Cr(3+) could, in fact, affect A1AT activity, in vitro studies were done to assess elastase inhibitory activity following A1AT incubation with soluble Cr(3+). In addition, to determine if Cr(3+) found in the lungs as detoxification products of inhaled hexavalent Cr (Cr(6+)) could affect A1AT in situ, lavages from the lungs of chromate-exposed rats were also analyzed for elastase inhibitory activity The in vitro results indicate that Cr(3+) ions clearly inhibited A1AT function, with an IC50 of 1.1 mM being estimated under the experimental conditions used. The in vivo results indicate that long-term inhalation (12 wk or longer) of chromate-bearing atmospheres also gave rise to significant (i.e., 50-70%) inhibition of the antielastase activity of A1AT. Together, these results clearly suggest that the Cr(3+) present in coal dusts could potentially act to inhibit A1AT activity in the lungs of miners and thereby promote the emphysematogenicity of SiO(2) or of other emphysematogens present as coconstituents in these dusts.

Although acute exposure to ozone (03*) has been shown to influence the severity and prevalence of airway hyperresponsiveness, information has been lacking on effects due to long-term exposure at relatively low exposure concentrations. The goals of this study were to determine whether long-term repeated ozone exposures could induce nonspecific hyperresponsiveness in normal, nonatopic (nonsensitized) animals, whether such exposure could exacerbate the preexisting hyperresponsive state in atopic (sensitized) animals, or both. The study was also designed to determine whether gender modulated airway responsiveness related to ozone exposure. Airway responsiveness was measured during and after exposure to 0.1 and 0.3 ppm ozone for 4 hours/day, 4 days/week for 24 weeks in normal, nonsensitized guinea pigs, in guinea pigs sensitized to an allergen (ovalbumin) prior to initiation of ozone exposures, and in animals sensitized concurrently with ozone exposures. Both male and female animals were studied. Ozone exposure did not produce airway hyperresponsiveness in nonsensitized animals. Ozone exposure did exacerbate airway hyperresponsiveness to specific and nonspecific bronchoprovocation in both groups of sensitized animals, and this effect persisted at least 4 weeks after the end of the exposures. Although the overall degree of airway responsiveness did differ between genders (males had more responsive airways than did females), the airway response to ozone exposure did not differ between the two groups. Ozone-induced effects upon airway responsiveness were not associated with the number of pulmonary eosinophils or with any chronic pulmonary inflammatory response. Levels of antigen-specific antibodies increased in sensitized animals, and a significant correlation was observed between airway responsiveness and antibody levels. The results of this study provide support for a role of ambient ozone exposure in exacerbation of airway dysfunction in persons with atopy.

While acute exposures to ozone (O(3)) can alter airway responsiveness, effects from long-term exposures at low concentrations are less clear. This study assessed whether such exposures could induce nonspecific hyperresponsiveness in nonatopic (nonsensitized) guinea pigs and/or could exacerbate the pre-existing hyperresponsive state in atopic (sensitized) animals, and whether gender was a factor modulating any effect of O(3). Responsiveness was measured during and following exposures to 0.1 and 0.3 ppm O(3) for 4 h/day, 4 days/wk for 24 wk in male and female nonsensitized animals, those sensitized to allergen (ovalbumin) prior to initiation of O(3) exposures, and those sensitized concurrently with exposures. Ozone did not produce hyperresponsiveness in nonsensitized animals, but did exacerbate hyperresponsiveness to both specific and nonspecific bronchoprovocation challenges in sensitized animals, an effect that persisted through at least 4 wk after exposures ended. Gender was not a factor modulating response to O(3). Induced effects on responsiveness were not associated with numbers of eosinophils in the lungs nor with any chronic pulmonary inflammatory response, but were correlated with antigen-specific antibodies in blood. This study supports a role for chronic O(3) exposure in the exacerbation of airways dysfunction in a certain segment of the general population, namely, those demonstrating atopy.