Search

BackgroundEmerging experimental evidence suggests that air pollution may contribute to development of obesity and diabetes, but studies of children are limited.ObjectivesWe hypothesized that pollution effects would be magnified after bariatric surgery for treatment of obesity, reducing benefits of surgery.MethodsIn 75 obese adolescents, excess weight loss (EWL), high-density lipoprotein (HDL) cholesterol, triglycerides, alkaline phosphatase (ALP) and hemoglobin A1c (HbA1c ) were measured prospectively at baseline and following laparoscopic adjustable gastric banding (LAGB). Residential distances to major roads and the average two-year follow-up exposure to particulate matter

Rationale: Avoiding excess health damages attributable to climate change is a primary motivator for policy interventions to reduce greenhouse gas emissions. However, the health benefits of climate mitigation, as included in the policy assessment process, have been estimated without much input from health experts. Objectives: In accordance with recommendations from the National Academies in a 2017 report on approaches to update the social cost of greenhouse gases (SC-GHG), an expert panel of 26 health researchers and climate economists gathered for a virtual technical workshop in May 2021 to conduct a systematic review and meta-analysis and recommend improvements to the estimation of health impacts in economic-climate models. Methods: Regionally resolved effect estimates of unit increases in temperature on net all-cause mortality risk were generated through random-effects pooling of studies identified through a systematic review. Results: Effect estimates and associated uncertainties varied by global region, but net increases in mortality risk associated with increased average annual temperatures (ranging from 0.1% to 1.1% per 1°C) were estimated for all global regions. Key recommendations for the development and utilization of health damage modules were provided by the expert panel and included the following: not relying on individual methodologies in estimating health damages; incorporating a broader range of cause-specific mortality impacts; improving the climate parameters available in economic models; accounting for socioeconomic trajectories and adaptation factors when estimating health damages; and carefully considering how air pollution impacts should be incorporated in economic-climate models. Conclusions: This work provides an example of how subject-matter experts can work alongside climate economists in making continued improvements to SC-GHG estimates.

Unhealthy levels of air pollution are breathed by billions of people worldwide, and air pollution is the leading environmental cause of death and disability globally. Efforts to reduce air pollution at its many sources have had limited success, and in many areas of the world, poor air quality continues to worsen. Personal interventions to reduce exposure to air pollution include avoiding sources, staying indoors, filtering indoor air, using face masks, and limiting physical activity when and where air pollution levels are elevated. The effectiveness of these interventions varies widely with circumstances and conditions of use. Compared with upstream reduction or control of emissions, personal interventions place burdens and risk of adverse unintended consequences on individuals. We review evidence regarding the balance of benefits and potential harms of personal interventions for reducing exposure to outdoor air pollution, which merit careful consideration before making public health recommendations with regard to who should use personal interventions and where, when, and how they should be used.

Rationale: Over the past year, the American Thoracic Society (ATS), led by its Environmental Health Policy Committee, has reviewed the most current air quality scientific evidence and has revised their recommendations to 8 μg/m 3 and 25 μg/m 3 for long- and short-term fine particulate matter (PM 2.5 ) and reaffirmed the recommendation of 60 ppb for ozone to protect the American public from the known adverse health effects of air pollution. The current U.S. Environmental Protection Agency (EPA) standards, in contrast, expose the American public to pollution levels that are known to result in significant morbidity and mortality. Objectives: To provide county-level estimates of annual air pollution-related health outcomes across the United States using the most recent federal air quality data, and to support the ATS's recent update to the long-term PM 2.5 recommended standard. This study is presented as part of the annual ATS/Marron Institute "Health of the Air" report. Methods: Daily air pollution values were obtained from the EPA's air quality system for monitored counties in the United States from 2017-2019. Concentration-response functions used in the EPA's regulatory review process were applied to pollution increments corresponding to differences between the rolling 3-year design values and ATS-recommended levels for long-term PM 2.5 (8 μg/m 3 ), short-term PM 2.5 (25 μg/m 3 ), and ground-level ozone (O 3 ; 60 ppb). Health impacts were estimated at the county level in locations with valid monitoring data. Results: Meeting ATS recommendations throughout the country prevents an estimated 14,650 (95% confidence interval [CI], 8,660-22,610) deaths; 2,950 (95% CI, 1,530-4,330) lung cancer incidence events; 33,100 (95% CI, 7,300-71,000) morbidities, and 39.8 million (95% CI, 14.6-63.3 million) impacted days annually. This prevents 11,850 more deaths; 2,580 more lung cancer incidence events; 25,400 more morbidities; and 27.2 million more impacted days than meeting EPA standards alone. Conclusions: Significant health benefits to be gained by U.S. communities that work to meet ATS-recommended air quality standards have now been identified under scenarios meeting the new ATS recommendation for long-term PM 2.5 (8 μg/m 3 ). The "Health of the Air" report presents an opportunity for air quality managers to quantify local health burdens and EPA officials to update their standards to reflect the latest science.

Air pollution poses a serious threat to children's respiratory health around the world. Satellite remote-sensing technology and air quality models can provide pollution data on a global scale, necessary for risk communication efforts in regions without ground-based monitoring networks. Several large centers, including NASA, produce global pollution forecasts that may be used alongside air quality indices to communicate local, daily risk information to the public. Here we present a health-based, globally applicable air quality index developed specifically to reflect the respiratory health risks among children exposed to elevated outdoor air pollution. Additive, excess-risk air quality indices were developed using 51 different coefficients derived from time-series health studies evaluating the impacts of ambient fine particulate matter, nitrogen dioxide, and ozone on children's respiratory morbidity outcomes. A total of four indices were created which varied based on whether or not the underlying studies controlled for co-pollutants and in the adjustment of excess risks of individual pollutants. Combined with historical estimates of air pollution provided globally at a 25 × 25 km 2 spatial resolution from the NASA's Goddard Earth Observing System composition forecast (GEOS-CF) model, each of these indices were examined in a global sample of 664 small and 140 large cities for study year 2017. Adjusted indices presented the most normal distributions of locally-scaled index values, which has been shown to improve associations with health risks, while indices based on coefficients controlling for co-pollutants had little effect on index performance. We provide the steps and resources need to apply our final adjusted index at the local level using freely-available forecasting data from the GEOS-CF model, which can provide risk communication information for cities around the world to better inform individual behavior modification to best protect children's respiratory health., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Poor air quality affects the health and wellbeing of large populations around the globe. Although source controls are the most effective approaches for improving air quality and reducing health risks, individuals can also take actions to reduce their personal exposure by staying indoors, reducing physical activity, altering modes of transportation, filtering indoor air, and using respirators and other types of face masks. A synthesis of available evidence on the efficacy, effectiveness, and potential adverse effects or unintended consequences of personal interventions for air pollution is needed by clinicians to assist patients and the public in making informed decisions about use of these interventions. To address this need, the American Thoracic Society convened a workshop in May of 2018 to bring together a multidisciplinary group of international experts to review the current state of knowledge about personal interventions for air pollution and important considerations when helping patients and the general public to make decisions about how best to protect themselves. From these discussions, recommendations were made regarding when, where, how, and for whom to consider personal interventions. In addition to the efficacy and safety of the various interventions, the committee considered evidence regarding the identification of patients at greatest risk, the reliability of air quality indices, the communication challenges, and the ethical and equity considerations that arise when discussing personal interventions to reduce exposure and risk from outdoor air pollution.

The combination of air quality (AQ) data from satellites and low-cost sensor systems, along with output from AQ models, have the potential to augment high-quality, regulatory-grade data in countries with in situ monitoring networks and provide much needed AQ information in countries without them, including Low and Moderate Income Countries (LMICs). We demonstrate the potential of free and publicly available USA National Aeronautics and Space Administration (NASA) resources, which include capacity building activities, satellite data, and global AQ forecasts, to provide cost-effective, and reliable AQ information to health and AQ professionals around the world. We provide illustrative case studies that highlight how global AQ forecasts along with satellite data may be used to characterize AQ on urban to regional scales, including to quantify pollution concentrations, identify pollution sources, and track the long-range transport of pollution. We also provide recommendations to data product developers to facilitate and broaden usage of NASA resources by health and AQ stakeholders., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2021 The Authors. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Wildland fires are diminishing air quality on a seasonal and regional basis, raising concerns about respiratory health risks to the public and occupational groups. This American Thoracic Society (ATS) workshop was convened in 2019 to meet the growing health threat of wildland fire smoke. The workshop brought together a multidisciplinary group of 19 experts, including wildland fire managers, public health officials, epidemiologists, toxicologists, and pediatric and adult pulmonologists. The workshop examined the following four major topics: 1 ) the science of wildland fire incidence and fire management, 2 ) the respiratory and cardiovascular health effects of wildland fire smoke exposure, 3 ) communication strategies to address these health risks, and 4 ) actions to address wildland fire health impacts. Through formal presentations followed by group discussion, workshop participants identified top priorities for fire management, research, communication, and public policy to address health risks of wildland fires. The workshop concluded that short-term exposure to wildland smoke causes acute respiratory health effects, especially among those with asthma and chronic obstructive pulmonary disease. Research is needed to understand long-term health effects of repeated smoke exposures across fire seasons for children, adults, and highly exposed occupational groups (especially firefighters). Other research priorities include fire data collection and modeling, toxicology of different fire fuel sources, and the efficacy of health protective measures to prevent respiratory effects of smoke exposure. The workshop committee recommends a unified federal response to the growing problem of wildland fires, including investment in fire behavior and smoke air quality modeling, research on the health impacts of smoke, and development of robust clinical and public health communication tools.

Background: The Air Quality Index (AQI) in the United States is widely used to communicate daily air quality information to the public. While use of the AQI has led to reported changes in individual behaviors, such behavior modifications will only mitigate adverse health effects if AQI values are indicative of public health risks. Few studies have assessed the capability of the AQI to accurately predict respiratory morbidity risks., Methods and Findings: In three major regions of California, Poisson generalized linear models were used to assess seasonal associations between 1,373,165 respiratory emergency department visits and short-term exposure to multiple metrics between 2012-2014, including: daily concentrations of NO2, O3, and PM2.5; the daily reported AQI; and a newly constructed health-based air quality index. AQI values were positively associated (average risk ratio = 1.03, 95% CI 1.02-1.04) during the cooler months of the year (November-February) in all three regions when the AQI was very highly correlated with PM2.5 (R2 ≥ 0.89). During the warm season (March-October) in the San Joaquin Valley region, neither AQI values nor the individual underlying air pollutants were associated with respiratory morbidity. Additionally, AQI values were not positively associated with respiratory morbidity in the Southern California region during the warm season, despite strong associations of the individual underlying air pollutants with respiratory morbidity; in contrast, health-based index values were observed to be significantly associated with respiratory morbidity as part of an applied policy analysis in this region, with a combined risk ratio of 1.02 (95% CI: 1.01-1.03)., Conclusions: In regions where individual air pollutants are associated with respiratory morbidity, and during seasons with relatively simple air mixtures, the AQI can effectively serve as a risk communication tool for respiratory health risks. However, the predictive ability of the AQI and any other index is contingent upon the monitored values being representative of actual population exposures. Other approaches, such as health-based indices, may be needed in order to effectively communicate health risks of air pollution in regions and seasons with more complex air mixtures., Competing Interests: The authors have declared that no competing interests exist.

Air quality data from satellites and low-cost sensor systems, together with output from air quality models, have the potential to augment high-quality, regulatory-grade data in countries with in situ monitoring networks and provide much-needed air quality information in countries without them. Each of these technologies has strengths and limitations that need to be considered when integrating them to develop a robust and diverse global air quality monitoring network. To address these issues, the American Thoracic Society, the U.S. Environmental Protection Agency, the National Aeronautics and Space Administration, and the National Institute of Environmental Health Sciences convened a workshop in May 2017 to bring together global experts from across multiple disciplines and agencies to discuss current and near-term capabilities to monitor global air pollution. The participants focused on four topics: 1 ) current and near-term capabilities in air pollution monitoring, 2 ) data assimilation from multiple technology platforms, 3 ) critical issues for air pollution monitoring in regions without a regulatory-quality stationary monitoring network, and 4 ) risk communication and health messaging. Recommendations for research and improved use were identified during the workshop, including a recognition that the integration of data across monitoring technology groups is critical to maximizing the effectiveness (e.g., data accuracy, as well as spatial and temporal coverage) of these monitoring technologies. Taken together, these recommendations will advance the development of a global air quality monitoring network that takes advantage of emerging technologies to ensure the availability of free, accessible, and reliable air pollution data and forecasts to health professionals, as well as to all global citizens.

Rationale: Air quality improvements are increasingly difficult to come by as modern pollution control technologies and measures have been widely implemented in the United States. Although there have been dramatic improvements in air quality over the last several decades, it is important to evaluate changes in the health impacts of air pollution for a more recent time period to better understand the current trajectory of air quality improvements. Objectives: To provide county-level estimates of annual air pollution-related health outcomes across the United States and to evaluate these trends from 2008 to 2017, presented as part of the annual American Thoracic Society (ATS)/Marron Institute "Health of the Air" report. Methods: Daily air pollution values were obtained from the U.S. Environmental Protection Agency's Air Quality System for monitors in the United States from 2008 to 2017. Concentration-response functions used in the ATS/Marron Institute "Health of the Air" report were applied to the pollution increments corresponding to differences between the rolling 3-year design values (reported as the third year) and ATS-recommended levels for annual particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM 2.5 ; 11 μg/m 3 ), short-term PM 2.5 (25 μg/m 3 ), and ozone (O 3 ; 60 ppb). Health impacts were estimated at the county level in locations with valid monitor data. Results: Annual excess mortality in the United States due to air pollution levels greater than recommended by the ATS decreased from approximately 12,600 (95% confidence interval [CI], 5,470-21,040) in 2010 to 7,140 (95% CI, 2,290-14,040) in 2017. This improvement can be attributed almost entirely to reductions in PM 2.5 -related mortality, which decreased by approximately 60% (reduced from 8,330 to 3,260 annual deaths), whereas O 3 -related mortality remained largely unchanged, other than year-to-year variability, over the same time period (reduced from 4,270 to 3,880 annual deaths). Conclusions: Improvements in health impacts attributable to ambient PM 2.5 concentrations have been observed across most regions of the United States over the last decade, although the rate of these improvements has leveled off in recent years. Despite two revisions of the National Ambient Air Quality Standards strengthening the standard for O 3 in 2008 and 2015, there has not yet been a substantial improvement in the health impacts attributable to O 3 during this time period. In many U.S. cities, an increase in the exposed population over the last decade has outpaced the improvements in ambient O 3 concentrations, resulting in a net increase in O 3 -related health impacts over time.

Background: The Mexico City Metropolitan Area has an expansive urban population and a long history of air quality management challenges. Poor air quality has been associated with adverse pulmonary and cardiac health effects, particularly among susceptible populations with underlying disease. In addition to reducing pollution concentrations, risk communication efforts that inform behavior modification have the potential to reduce public health burdens associated with air pollution., Methods: This study investigates the utilization of Mexico's IMECA risk communication index to inform air pollution avoidance behavior among the general population living in the Mexico City Metropolitan Area. Individuals were selected via probability sampling and surveyed by phone about their air quality index knowledge, pollution concerns, and individual behaviors., Results: The results indicated reasonably high awareness of the air quality index (53% of respondents), with greater awareness in urban areas, among older and more educated individuals, and for those who received air quality information from a healthcare provider. Additionally, behavior modification was less influenced by index reports as it was by personal perceptions of air quality, and there was no difference in behavior modification among susceptible and non-susceptible groups., Conclusions: Taken together, these results suggest there are opportunities to improve the public health impact of risk communication through an increased focus on susceptible populations and greater encouragement of public action in response to local air quality indices.

Inhalation of ozone (O 3 ), a gaseous air pollutant, causes lung injury, lung inflammation, and airway hyperresponsiveness. Macrophages, mast cells, and neutrophils contribute to one or more of these sequelae induced by O 3 Furthermore, each of these aforementioned cells express chemokine (C-C motif) receptor-like 2 (Ccrl2), an atypical chemokine receptor that facilitates leukocyte chemotaxis. Given that Ccrl2 is expressed by cells essential to the development of O 3 -induced lung pathology and that chemerin, a Ccrl2 ligand, is increased in bronchoalveolar lavage fluid (BALF) by O 3 , we hypothesized that Ccrl2 contributes to the development of lung injury, lung inflammation, and airway hyperresponsiveness induced by O 3 To that end, we measured indices of lung injury (BALF protein, BALF epithelial cells, and bronchiolar epithelial injury), lung inflammation (BALF cytokines and BALF leukocytes), and airway responsiveness to acetyl- β -methylcholine chloride (respiratory system resistance) in wild-type and mice genetically deficient in Ccrl2 (Ccrl2-deficient mice) 4 and/or 24 hours following cessation of acute exposure to either filtered room air (air) or O 3 In air-exposed mice, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O 3 increased BALF chemerin in mice of both genotypes, yet following O 3 exposure, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O 3 increased indices of lung injury, lung inflammation, and airway responsiveness. Nevertheless, no indices were different between genotypes following O 3 exposure. In conclusion, we demonstrate that Ccrl2 modulates chemerin levels in the epithelial lining fluid of the lungs but does not contribute to the development of O 3 -induced lung pathology., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O 3 ), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O 3 Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O 3 To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O 3 (2 ppm) for 3 h. Four and/or twenty-four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL-6, KC, MIP-2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl-β-methylcholine chloride (respiratory system resistance) were measured in wild-type and PAI-1-deficient mice. O 3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild-type and PAI-1-deficient mice. With the exception of MIP-2, which was significantly lower in PAI-1-deficient as compared to wild-type mice 24 h following cessation of exposure to O 3 , no other genotype-related differences occurred subsequent to O 3 exposure. Thus, following acute exposure to O 3 , PAI-1 neither regulates pulmonary expression of IL-6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O 3 ., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Estimates of the health impacts of air pollution are needed to make informed air quality management decisions at both the national and local levels. Using design values of ambient pollution concentrations from 2011-2013 as a baseline, the American Thoracic Society (ATS) and the Marron Institute of Urban Management estimated excess morbidity and mortality in the United States attributable to exposure to ambient ozone (O3) and fine particulate matter (PM2.5) at levels above the American Thoracic Society-recommended standards. Within the subset of counties with valid design values for each pollutant, 14% had PM2.5 concentrations greater than the ATS recommendation, whereas 91% had O3 concentrations greater than the ATS recommendation. Approximately 9,320 excess deaths (69% from O3; 31% from PM2.5), 21,400 excess morbidities (74% from O3; 26% from PM2.5), and 19,300,000 adversely impacted days (88% from O3; 12% from PM2.5) in the United States each year are attributable to pollution exceeding the ATS-recommended standards. California alone is responsible for 37% of the total estimated health impacts, and the next three states (Pennsylvania, Texas, and Ohio) together contributed to 20% of the total estimates. City-specific health estimates are provided in this report and through an accompanying online tool to help inform air quality management decisions made at the local level. Riverside and Los Angeles, California have the most to gain by attaining the ATS recommendations for O3 and PM2.5. This report will be revised and updated regularly to help cities track their progress.

Background: Outdoor fine particulate matter (≤ 2.5 μm; PM2.5) has been identified as a global health threat, but the number of large U.S. prospective cohort studies with individual participant data remains limited, especially at lower recent exposures., Objectives: We aimed to test the relationship between long-term exposure PM2.5 and death risk from all nonaccidental causes, cardiovascular (CVD), and respiratory diseases in 517,041 men and women enrolled in the National Institutes of Health-AARP cohort., Methods: Individual participant data were linked with residence PM2.5 exposure estimates across the continental United States for a 2000-2009 follow-up period when matching census tract-level PM2.5 exposure data were available. Participants enrolled ranged from 50 to 71 years of age, residing in six U.S. states and two cities. Cox proportional hazard models yielded hazard ratio (HR) estimates per 10 μg/m3 of PM2.5 exposure., Results: PM2.5 exposure was significantly associated with total mortality (HR = 1.03; 95% CI: 1.00, 1.05) and CVD mortality (HR = 1.10; 95% CI: 1.05, 1.15), but the association with respiratory mortality was not statistically significant (HR = 1.05; 95% CI: 0.98, 1.13). A significant association was found with respiratory mortality only among never smokers (HR = 1.27; 95% CI: 1.03, 1.56). Associations with 10-μg/m3 PM2.5 exposures in yearly participant residential annual mean, or in metropolitan area-wide mean, were consistent with baseline exposure model results. Associations with PM2.5 were similar when adjusted for ozone exposures. Analyses of California residents alone also yielded statistically significant PM2.5 mortality HRs for total and CVD mortality., Conclusions: Long-term exposure to PM2.5 air pollution was associated with an increased risk of total and CVD mortality, providing an independent test of the PM2.5-mortality relationship in a new large U.S. prospective cohort experiencing lower post-2000 PM2.5 exposure levels., Citation: Thurston GD, Ahn J, Cromar KR, Shao Y, Reynolds HR, Jerrett M, Lim CC, Shanley R, Park Y, Hayes RB. 2016. Ambient particulate matter air pollution exposure and mortality in the NIH-AARP Diet and Health cohort. Environ Health Perspect 124:484-490; http://dx.doi.org/10.1289/ehp.1509676.

Background: Long-term exposure to ambient particulate matter (PM) air pollution is associated with increased cardiovascular disease (CVD); however, the impact of PM on clinical risk factors for CVD in healthy subjects is unclear. We examined the relationship of PM with levels of circulating lipids and blood pressure in the Third National Health and Nutrition Examination Survey (NHANES III), a large nationally representative US survey., Methods: This study was based on 11,623 adult participants of NHANES III (1988-1994; median age 41.0). Serum lipids and blood pressure were measured during the NHANES III examination. Average exposure for 1988-1994 to particulate matter <10 μm in aerodynamic diameter (PM10) at the residences of participants was estimated based on measurements from US Environmental Protection Agency monitors. Multivariate linear regression was used to estimate the associations of PM10 with lipids and blood pressure., Results: An interquartile range width increase in PM10 exposure (11.1 μg/m) in the study population was associated with 2.42% greater serum triglycerides (95% confidence interval: 1.09, 3.76); multivariate adjusted means of triglycerides according to increasing quartiles of PM10 were 137.6, 142.5, 142.6, and 148.9 mg/dl, respectively. An interquartile range width increase in PM10 was associated with 1.43% greater total cholesterol (95% confidence interval: 1.21, 1.66). These relationships with triglycerides and total cholesterol did not differ by age or region. Associations of PM10 with blood pressure were modest., Conclusions: Findings from this large, diverse study indicate that greater long-term PM10 exposure is associated with elevated serum triglycerides and total cholesterol, potentially mediating air pollution-related effects on CVD.

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology., (Copyright © 2015 the American Physiological Society.)

Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin (ob/ob mice) or the long isoform of the leptin receptor (db/db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure (Cpe(fat) mice). Accordingly, Cpe(fat) and lean, wild-type (C57BL/6) mice were sensitized to OVA and then challenged with either aerosolized PBS or OVA. Compared with genotype-matched, OVA-sensitized and PBS-challenged mice, OVA sensitization and challenge elicited airway obstruction and increased BALF eosinophils, macrophages, neutrophils, IL-4, IL-13, IL-18, and chemerin. However, OVA challenge enhanced airway obstruction and pulmonary inflammation in Cpe(fat) compared with wild-type mice. These results demonstrate that OVA sensitization and challenge enhance airway obstruction in obese mice regardless of the genetic basis of obesity, whereas the degree of OVA-induced pulmonary inflammation is dependent on the genetic modality of obesity induction. These results have important implications for animal models of asthma, as modeling the pulmonary phenotypes for subpopulations of atopic, obese asthmatics critically depends on selecting the appropriate mouse model., (Copyright © 2014 the American Physiological Society.)

Inhalation of ozone (O₃), a common environmental pollutant, causes pulmonary injury, pulmonary inflammation, and airway hyperresponsiveness (AHR) in healthy individuals and exacerbates many of these same sequelae in individuals with preexisting lung disease. However, the mechanisms underlying these phenomena are poorly understood. Consequently, we sought to determine the contribution of osteopontin (OPN), a hormone and a pleiotropic cytokine, to the development of O₃-induced pulmonary injury, pulmonary inflammation, and AHR. To that end, we examined indices of these aforementioned sequelae in mice genetically deficient in OPN and in wild-type, C57BL/6 mice 24 h following the cessation of an acute (3 h) exposure to filtered room air (air) or O₃ (2 parts/million). In wild-type mice, O₃ exposure increased bronchoalveolar lavage fluid (BALF) OPN, whereas immunohistochemical analysis demonstrated that there were no differences in the number of OPN-positive alveolar macrophages between air- and O₃-exposed wild-type mice. O₃ exposure also increased BALF epithelial cells, protein, and neutrophils in wild-type and OPN-deficient mice compared with genotype-matched, air-exposed controls. However, following O₃ exposure, BALF neutrophils were significantly reduced in OPN-deficient compared with wild-type mice. When airway responsiveness to inhaled acetyl-β-methylcholine chloride (methacholine) was assessed using the forced oscillation technique, O₃ exposure caused hyperresponsiveness to methacholine in the airways and lung parenchyma of wild-type mice, but not OPN-deficient mice. These results demonstrate that OPN is increased in the air spaces following acute exposure to O₃ and functionally contributes to the development of O₃-induced pulmonary inflammation and airway and lung parenchymal hyperresponsiveness to methacholine.

We describe spatial and temporal patterns of seven chemical elements commonly observed in fine particulate matter (PM) and thought to be linked to roadway emissions that were measured at residential locations in New York City (NYC). These elements, that is, Si, Al, Ti, Fe, Ba, Br, and black carbon (BC), were found to have significant spatial and temporal variability at our 10 residential PM(2.5) sampling locations. We also describe pilot study data of near-roadway samples of both PM(10-2.5) and PM(2.5) chemical elements of roadway emissions. PM(2.5) element concentrations collected on the George Washington Bridge (GWB) connecting NYC and New Jersey were higher that similar elemental concentration measured at residential locations. Coarse-particle elements (within PM(10-2.5)) on the GWB were 10-100 times higher in concentration than their PM(2.5) counterparts. Roadway elements were well correlated with one another in both the PM(2.5) and PM(10-2.5) fractions, suggesting common sources. The same elements in the PM(2.5) collected at residential locations were less correlated, suggesting either different sources or different processing mechanisms for each element. Despite the fact that these elements are only a fraction of total PM(2.5) or PM(10-2.5) mass, the results have important implications for near-roadway exposures where elements with known causal links to health effects are shown to be at elevated concentrations in both the PM(2.5) and PM(10-2.5) size ranges.

Palmitoyl-lysophosphatidylcholine promotes a transient calcium influx in lymphoma cells. Previously, it was observed that this influx was accompanied by a temporary increase in propidium iodide permeability that appeared linked to calcium entry. Those studies demonstrated that cobalt or nickel could block the response to lysophosphatidylcholine and raised the question of whether the calcium conductance involved specific channels. This communication describes a series of experiments to address that issue. The time dependence and structural specificity of the responses to lysophosphatidylcholine reinforced the hypothesis of a specific channel or transporter. Nevertheless, observations using patch clamp or calcium channel blockers suggested that this "channel" does not involve proteins. Alternative protein-mediated mechanisms such as indirect involvement of the sodium-calcium exchanger and the sodium-potassium ATPase were also excluded. Experiments with extracellular and intracellular calcium chelators suggested a common route of entry for calcium and propidium iodide. More directly, the ability of lysophosphatidylcholine to produce cobalt-sensitive permeability to propidium iodide was reproduced in protein-free artificial membranes. Finally, the transient nature of the calcium time course was rationalized quantitatively by the kinetics of lysophosphatidylcholine metabolism. These results suggest that physiological concentrations of lysophosphatidylcholine can directly produce membrane pores that mimic some of the properties of specific protein channels.