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Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and its global health burden is increasing. COPD is characterized by emphysema, mucus hypersecretion, and persistent lung inflammation, and clinically by chronic airflow obstruction and symptoms of dyspnea, cough, and fatigue in patients. A cluster of pathologies including chronic bronchitis, emphysema, asthma, and cardiovascular disease in the form of hypertension and atherosclerosis variably coexist in COPD patients. Underlying causes for COPD include primarily tobacco use but may also be driven by exposure to air pollutants, biomass burning, and workplace related fumes and chemicals. While no single animal model might mimic all features of human COPD, a wide variety of published models have collectively helped to improve our understanding of disease processes involved in the genesis and persistence of COPD. In this review, the pathogenesis and associated risk factors of COPD are examined in different mammalian models of the disease. Each animal model included in this review is exclusively created by tobacco smoke (TS) exposure. As animal models continue to aid in defining the pathobiological mechanisms of and possible novel therapeutic interventions for COPD, the advantages and disadvantages of each animal model are discussed.

The induction of immunological responses that trigger bio-physiological symptoms in the respiratory tract following repeated exposure to a substance, is known as respiratory sensitization. The inducing compound is known as a respiratory sensitizer. While respiratory sensitization by high molecular weight (HMW) materials is recognized and extensively studied, much less information is available regarding low molecular weight (LMW) materials as respiratory sensitizers. Variability of symptoms presented in humans from such exposures, limited availability of (and access to) documented reports, and the absence of standardized and validated test models, hinders the identification of true respiratory sensitizers. This review aims to sort suspected LMW respiratory sensitizers based on available compelling, reasonable, inadequate, or questionable evidence in humans from occupational exposures and use this information to compose a reference list of reported chemical respiratory sensitizers for scientific research purposes. A list of 97 reported respiratory sensitizers was generated from six sources, and 52 LMW organic chemicals were identified, reviewed, and assigned to the four evidence categories. Less than 10 chemicals were confirmed with compelling evidence for induction of respiratory sensitization in humans from occupational exposures. Here, we propose the reference list for developing novel research on respiratory sensitization.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and has been associated with periods of intense lung inflammation. The objective of this study was to characterize whether similar rat strains, possessing different genetic predispositions, might play a role in exacerbating the pathophysiology of COPD-like cellular and structural changes with progressive 12-week exposure to tobacco smoke (TS). Normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats were compared. MATERIALS AND METHODS: WKY and SH rats were exposed to filtered air or to tobacco smoke at a particulate concentration of 80 mg/m(3) for 4, 8, or 12 weeks. Necropsy was performed 24 hours after the last exposure to obtain cells by bronchoalveolar lavage for total cell and differential counts. Scoring of lung tissues and immunohistochemical staining for M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages were performed on paraffin-embedded lung sections. RESULTS AND DISCUSSION: With progressive exposure, TS-exposed SH rats demonstrated significant airspace enlargement, mucin production, and lung inflammation compared to their FA control and TS-matched WKY rats. Moreover, SH rats also demonstrated increased expression of the M1 marker in alveolar macrophages compared to FA control, as well as the M2 marker compared to controls and TS-exposed WKY rats. CONCLUSION: The progressive tobacco smoke exposure contributes to persistent lung injury and inflammation that can be significantly enhanced by rat strain susceptibility in the genesis of COPD.

Objective: The study examines how wildfire smoke exposure may impact health and safety in the agricultural workplace.Methods: Semi-structured interviews were conducted with agricultural employers a...

OBJECTIVE: The Western Center for Agricultural Health and Safety (WCAHS) at the University of California, Davis implemented a multifaceted rapid response to COVID-19 in the western United States. This paper describes the center's response from mid-March through June 30, 2020. METHODS: A comprehensive needs assessment was conducted with agricultural stakeholders. Agriculture-specific COVID-19 resources were developed and disseminated, and a farmer/employer survey was launched. RESULTS: The WCAHS COVID-19 resources web page, worksite checklist, and training guide were shared on over 50 web pages nationally. As of June 30, 2020, 282 online surveys have been received. Ongoing informal discussions with agricultural stakeholders indicate a disconnect between the experiences of farmers/employers and farmworkers in relation to COVID-19 prevention at the worksite. Initial survey responses indicate that implementing social distancing is one of the greatest challenges at the worksite. Confusion over local, state, and federal guidelines and which to follow is another concern. CONCLUSION: The WCAHS response to COVID-19, in close collaboration with agricultural stakeholders, represents a useful model for a rapid response to a public health crisis by regional centers. Key elements to its success include rapid personalized communication with a wide range of agricultural stakeholders, an actively engaged External Advisory Board, the development of industry-specific resources and information, recurring and iterative engagement with stakeholders as new COVID-19 information emerged and resources were developed, and the identification of the unique gap WCAHS was positioned to fill. The multipronged dissemination approach enhanced the reach of WCAHS COVID-19 resources.

Ambient particulate matter (PM), a component of air pollution, exacerbates airway inflammation and hyperreactivity in asthmatic patients. Studies showed that PM possesses adjuvant-like properties that enhance the allergic inflammatory response; however, the mechanism (or mechanisms) by which PM enhances the allergic response remains to be determined. The aim of this study was to assess how exposure to fine PM collected from Sacramento, CA, shapes the allergic airway immune response in BALB/c mice undergoing sensitization and challenge with ovalbumin (OVA). Eight-week-old BALB/c male mice were sensitized/challenged with phosphate-buffered saline (PBS/PBS; n = 6), PM/PBS (n = 6), OVA/OVA (n = 6), or OVA + PM/OVA (n = 6). Lung tissue, bronchoalveolar lavage fluid (BALF), and plasma were analyzed for cellular inflammation, cytokines, immunoglobulin E, and heme oxygenase-1 (HO-1) expression. Mice in the OVA + PM/OVA group displayed significantly increased airway inflammation compared to OVA/OVA animals. Total cells, macrophages, and eosinophils recovered in BALF were significantly elevated in the OVA + PM/OVA compared to OVA/OVA group. Histopathological grading indicated that OVA + PM/OVA treatment induced significant inflammation compared to OVA/OVA. Both immunoglobulin (Ig) E and tumor necrosis factor (TNF) α levels were significantly increased in OVA/OVA and OVA + PM /OVA groups compared to PBS/PBS control. The number of HO-1 positive alveolar macrophages was significantly elevated in lungs of mice treated with OVA + PM /OVA compared to OVA/OVA. Our findings suggest that fine PM enhances allergic inflammatory response in pulmonary tissue through mechanisms involving increased oxidative stress.

Approximately four million people die every year from chronic obstructive pulmonary disease (COPD), with more than 80% of the cases attributed to smoking.The purpose of this study was to examine the rat strain and sex-related differences and the extended tobacco smoke exposure to induce lung injury and inflammation with the goal of finding a suitable rodent model to study COPD.Male and female spontaneously hypertensive (SH) and male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or to tobacco smoke (TS: 90 mg/mMale SH rats demonstrated an enhanced, persistent inflammatory response compared to female SH and male WKY rats with extended TS exposure. Following four weeks of TS exposure, male SH rats had significantly increased total leukocytes and macrophage numbers, levels of TNF-alpha and elevated lactate dehydrogenase activity in bronchoalveolar lavage fluid compared with female SH, male WKY rats and corresponding controls. After 12 weeks of TS exposure, male SH rats continued to show significant increase in inflammatory cells and TNF-alpha, as well as IL-6 mRNA lung expression. In addition, the alveolar airspace of male SH rats exposed to TS was significantly enlarged compared to their FA controls, female SH and WKY rats.The male SH rat demonstrates greater cellular, inflammatory and structural changes highly reminiscent of COPD compared to female SH and male WKY rats, suggesting that the male SH rat is an optimal rodent model to study COPD.

Titanium dioxide (TiO2) is one of the most widely used nanomaterials, valued for its highly refractive, photocatalytic, and pigmenting properties. TiO2 is also classified by the International Agency for Research on Cancer (IARC) as a possible human carcinogen. The objectives of this study were to (1) establish a lowest-observed-effect level (LOEL) for nano-scale TiO2, (2) determine TiO2 uptake in the lungs, and (3) estimate toxicity based on physicochemical properties and retention in the lungs. In vivo lung toxicity of nano-scale TiO2 using varying forms of well-characterized, highly dispersed TiO2 was assessed. Anatase/rutile P25 spheres (TiO2-P25), pure anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NB) were tested. To determine the effects of dose and particle characteristics, male Sprague-Dawley rats were administered TiO2 (0, 20, 70, or 200 μg) via intratracheal instillation. Bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for analysis 1 and 7 d post exposure. Despite abundant TiO2 inclusions in all exposed animals, only TiO2-NB displayed any significant degree of inflammation seen in BALF at the 1-d time point. This inflammation resolved by 7 d, although TiO2 particles had not cleared from alveolar macrophages recovered from the lung. Histological examination showed TiO2-NB produced cellular changes at d 1 that were still evident at d 7. Data indicate TiO2-NB is the most inflammatory with a LOEL of 200 μg at 1 d post instillation.

Assessing the human health risks associated with engineered nanomaterials is challenging because of the wide range of plausible exposure scenarios. While exposure to nanomaterials may occur through a number of pathways, inhalation is likely one of the most significant potential routes of exposure in industrial settings. An aerosolization system was developed to administer carbon nanomaterials from a dry bulk medium into airborne particles for delivery into a nose-only inhalation system. Utilization of a cannula-based feed system, diamond-coated wheel, aerosolization chamber, and krypton-85 source allows for delivery of otherwise difficult to produce respirable-sized particles. The particle size distribution (aerodynamic and actual) and morphology were characterized for different aerosolized carbon-based nanomaterials (e.g., single-walled carbon nanotubes and ultrafine carbon black). Airborne particles represented a range of size and morphological characteristics, all of which were agglomerated particles s...

Greater risk of adverse effects from particulate matter (PM) has been noted in susceptible subpopulations, such as children. However, the physicochemical components responsible for these biological effects are not understood. As critical constituents of PM, transition metals were postulated to be involved in a number of pathological processes of the respiratory system through free radical-medicated damage. The purpose of this study was to examine whether oxidative injury in the lungs of neonatal rats could be induced by repeated short-term exposure to iron (Fe) and soot particles. Sprague Dawley rats 10 d of age were exposed by inhalation to two different concentrations of ultrafine iron particles (30 or 100 microg/m(3)) in combination with soot particles adjusted to maintain a total particle concentration of 250 microg/m(3). Exposure at 10 d and again at 23 d of age was for 6 h/d for 3 d. Oxidative stress was observed at both Fe concentrations in the form of significant elevations in glutathione disulfide (GSSG) and GSSG/glutathione (GSH) ratio and a reduction in ferric/reducing antioxidant power in bronchoalveolar lavage. A significant decrease in cell viability associated with significant increases in lactate dehydrogenase (LDH) activity, interleukin-1-beta (IL-1beta), and ferritin expression was noted following exposure to particles containing the highest Fe concentration. Iron from these particles was shown to be bioavailable in an in vitro assay using the physiologically relevant chelator, citrate. Data indicate that combined Fe and soot particle exposure induces oxidative injury, cytotoxicity and pro-inflammatory responses in the lungs of neonatal rats.

Increasingly, evidence suggests a role for a systemic procoagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation of airborne particulate matter. The authors evaluated blood cell parameters and markers of platelet activation in mice exposed to concentrated ambient particulate matter (CAPs) from the San Joaquin Valley of California, a region with severe particulate matter (PM) pollution episodes. The authors exposed mice to an average of 88.5 microg/m(3) of CAPs in a size range less than 2.5 microm for 6 h/day for 5 days per week for 2 weeks. Platelets were analyzed by flow cytometry for relative size, shape, aggregation, fibrinogen binding, P-selectin, and lysosomal-associated membrane protein-1 (LAMP-1) expression. Serum cytokines were analyzed by bead-based immunologic assays. CAPs-exposed mice had elevations in macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNFalpha), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF)-bb, and RANTES (regulated upon activation, normally T-expressed, and presumably secreted). Platelets were the only peripheral blood cells that were significantly elevated in number in CAPs-exposed mice. Flow cytometric analysis of unstimulated platelets from CAPs-exposed mice indicated size and shape changes, and platelets from CAPs-exposed animals had a 54% increase in fibrinogen binding indicative of platelet priming. Stimulation of platelets by thrombin resulted in up-regulation of LAMP-1 expression in CAPs-exposed animals and an increased microparticle population relative to control animals. These findings demonstrate a systemic proinflammatory and procoagulant response to inhalation of environmentally derived fine and ultrafine PM and suggests a role for platelet activation in the cardiovascular and respiratory effects of particulate air pollution.

This report summarizes discussions chaired by Kent Pinkerton held during the New Paths: Health and Safety in Western Agriculture conference, November 11-13, 2008. Research on air quality and aerosols in the agricultural setting was presented and discussed, providing insight into critical issues by many of the prominent scientists in this field. The panel discussion provided an overview of recent advances and future directions for research regarding sampling and exposure assessment of biologically active aerosols. This analysis considers chemical composition, individual exposures, and subsequent health effects experienced in large- and small-scale farming operations. The breakout discussion focused on other sources of particulate matter associated with agricultural activities prominent in various regions of the western United States. The complementary directions for these discussions fully demonstrate the wide range of concerns and issues that exist regarding bioaerosols and ambient dust associated with agricultural activities.

Exposure to cigarette smoke impairs the pulmonary immune system, including alveolar macrophage function, although the mechanisms by which this occurs are not fully elucidated. This study investigates the effect of cigarette smoke exposure on the antigen-presenting activity of alveolar macrophages, which is required for antigen-specific response to T cells. C57BL/6 mice were exposed to cigarette smoke for 10 days using a Hamburg II smoking machine, and alveolar macrophages were obtained by bronchoalveolar lavage. The antigen-presenting activity of alveolar macrophages was significantly inhibited in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. Major histocompatibility complex class II cell surface molecule-positive cells, B7-1 molecule-positive cells, and interleukin-1beta messenger RNA gene expression in alveolar macrophages were significantly decreased in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. In contrast, DNA damage and generation of superoxide and hydrogen peroxide in alveolar macrophages were significantly increased by cigarette smoke exposure. These results suggest that inhibition of the antigen-presenting activity of alveolar macrophages may result from decreased expression of major histocompatibility complex class II and B7-1 molecules and interleukin-1beta messenger RNA gene expression following cigarette smoke exposure. Furthermore, inhibition of antigen presentation in alveolar macrophage may result from DNA damage induced by excessive amounts of reactive oxygen species being generated by alveolar macrophages following cigarette smoke exposure. These findings suggest that cigarette smoke impairs the immunological function of alveolar macrophages and, as a result, increases the risk for pulmonary infection.

Approximately 15% of cases of COPD occur in non-smokers. Among the potential risk factors for COPD in non-smokers is second-hand smoke (SHS) exposure. However, the Surgeon General reported in 2006 that the evidence linking second hand smoke and COPD is insufficient to infer a causal relationship, largely because current evidence does not establish a biological link. The goal of this study was to determine whether SHS exposure can induce alveolar macrophage recruitment and expression of activation markers that we have previously demonstrated in human smokers and in mouse models of emphysema. To achieve these goals, we studied mice exposed to an ambient mixture of predominantly [89%] sidestream smoke at increasing doses over 3 months. We found that second hand smoke exposure induced a dose-dependent increase in alveolar macrophage recruitment (mean +/- sd; 224,511 +/- 52,330 vs 166,152 +/- 47,989 macrophages/ml of bronchoalveolar lavage in smoke-exposed vs air-exposed controls at 3 months, p = 0.003). We also found increased expression of several markers of alveolar macrophage activation (PLA2g7, dkfzp434l142, Trem-2, and pirin, all p < 0.01 at 3 months) and increased lavage levels of two inflammatory mediators associated with COPD (CCL2 [MCP-1], 58 +/- 12 vs. 43 +/- 22 pg/ml, p = 0.03; and TNFalpha, 138 +/- 43 vs 88 +/- 78 pg/ml, p = 0.04 at 3 months). These findings indicate that second smoke exposure can cause macrophage recruitment and activation, providing a biological link between second-hand smoke exposure and the development of inflammatory processes linked to COPD.

Exposure to environmental tobacco smoke (ETS) is known to contribute to and exacerbate inflammatory diseases of the lung such as chronic obstructive pulmonary disease (COPD) and asthma. The effect of ETS on angiogenesis and leukocyte recruitment, both of which promote lung inflammation, was investigated using lung tissue from mice exposed to aged and diluted sidestream cigarette smoke or fresh air for 12 weeks and transplanted into dorsal skin-fold chambers in nude mice. Lung tissue from mice exposed to cigarette smoke for 12 weeks exhibited significantly increased vascular density (angiogenesis) associated with selectin-mediated increased intravascular leukocyte rolling and adhesion compared to fresh air–exposed lung tissue by intravital microscopy. Further, neutrophils from nicotine-exposed mice displayed significantly increased rolling and adhesion compared to control neutrophils in microvessels of nicotine-exposed lungs versus control lung microvessels, suggesting that nicotine in cigarette smoke can augment leukocyte-endothelial interactions. ETS-induced angiogenesis and leukocyte trafficking may play a key role in airway recruitment of inflammatory cells in ETS-associated disorders such as COPD bronchitis or asthma.

Chronic exposure to tobacco smoke is known to impair mitochondrial function. However, the effect of acute tobacco smoke exposure (ATSE) in vivo, as might occur in social settings, on mitochondrial function and calcium handling of cardiac cells has not been examined. It was hypothesized that ATSE might adversely modify mitochondrial function as reflected in mitochondrial energetics, membrane potential, and calcium transport. Mitochondria were isolated from the hearts of adult rats either exposed to 6 h of environmental tobacco smoke ( approximately 60 mg/mm3 tobacco smoke particles) or sham exposure. To model a calcium stress similar to ischemia/reperfusion, mitochondria were exposed to a Ca2+ bolus with measurement of membrane potential, energetics, Ca2+uptake and release, and redox state. ATSE mitochondria were characterized by significantly higher ADP-stimulated ATP production and a more reduced redox state (NADH ratio) under basal conditions without observed changes in resting Psim. Exposure of ATSE mitochondria to Ca2+stress resulted in significantly more rapid depolarization of Psim. The initial rate of Ca2+uptake was not altered in ATSE mitochondria, but CsA-sensitive Ca2+ release was significantly increased. ATSE does not significantly alter resting mitochondrial function. However, ATSE modifies the response of cardiac mitochondria to calcium stress, resulting in a more rapid depolarization and subsequent release of Ca2+ via the mitochondrial permeability transition (MPT).

A novel design for a dry-aerosol generator that efficiently produces a well-dispersed dust suspension using small quantities of a PM2.5-enriched powder sample is described. The motivation to develop a highly efficient dry-aerosol particle generator was to facilitate collaborative projects that combine in vitro cell culture experiments and multiday inhalation exposures using a single batch of well-characterized particles. Premixing of the test particles with larger diameter glass beads permits delivery of aerosol concentrations from 100–1000 μ g/m3 to an exposure chamber using only milligram quantities of the test powder per hour. Examination of exposure chamber filter samples by scanning electron microscopy showed well-dispersed particles of the test powder free of glass spheres or fragments. Data are presented from experiments using coal fly ash as the test powder to illustrate the system performance.

A murine model of allergen-induced airway inflammation was used to examine the effects of exposure to ultrafine particles (PM(2.5)) on airway inflammation and remodeling. Lung inflammation was measured by quantitative differential evaluation of lung lavage cells. Alterations in lung structure (airway remodeling and fibrosis) were evaluated by quantitative biochemical analysis of microdissected airways and by histological evaluation of stained lung sections. The same total number of cells was observed in lavage fluid from animals exposed for 4 wk to ovalbumin alone or to ovalbumin for 4 wk immediately before or after 6 exposures over a period of 2 wk to 235 ug/m(3) of PM(2.5). Mice exposed to ovalbumin for 6 wk with concurrent exposure to PM(2.5) during wk 5-6 had a significant decrease in the total number of cells recovered by lavage as compared with the group exposed to ovalbumin alone. There were no significant differences in the cell differential counts in the lavage fluid from mice exposed to ovalbumin alone as compared with values from mice exposed to ovalbumin and PM(2.5) under the protocols studied. Airway structural changes (remodeling) were examined by three different quantitative methods. None of the groups exposed to ovalbumin and PM had a significant increase in airway collagen content evaluated biochemically (i.e., total airway collagen) as compared to the matched groups of mice exposed to ovalbumin alone. Airway collagen content evaluated histologically by sirius red staining showed significant increases in all of the animals exposed to ovalbumin, with or without PM, and no apparent difference between the ovalbumin group and mice exposed to PM with ovalbumin. The findings were consistent with an additive, or less than additive, response of mice to exposure to PM and ovalbumin. Air or PM exposure alone for 2 wk did not result in observable goblet cells in the airways, while mice exposed to ovalbumin aerosol alone for 4 wk had about 20-25% goblet cells in their conducting airways. Sequential exposure to ovalbumin and PM (or vice versa) caused significant increases in goblet cells (to about 35% of total cells) in the conducting airways of the exposed mice. We conclude that when mice with allergen-induced airway inflammation induced by ovalbumin are also exposed to PM(2.5), the lung inflammatory response and airway remodeling may be modified, but that this altered response is dependent upon the sequence of exposure and the duration of exposure to ovalbumin aerosol. At the concentrations of PM tested, we did not see changes in airway fibrosis or airway reactivity for animals exposed to ovalbumin and PM(2.5) as compared with animals exposed only to ovalbumin aerosol. However, goblet-cell hyperplasia was significantly increased in mice exposed concurrently to ovalbumin and PM(2.5) as compared with mice exposed to ovalbumin alone.

A diffusion flame system was used to generate an aerosol of soot and iron oxide. The primary fuel was ethylene. Iron was introduced by passing ethylene over liquid iron pentacarbonyl. The aerosol emission from the flame was diluted by secondary air to a level that could be used in animal exposure studies. The system was designed to operate at a constant soot production rate while the iron loading was varied from 0 to 50 μg m -3 in the diluted postflame gases. The impact of the iron on soot production was counteracted by the addition of acetylene to the fuel. Particles were collected on carbon grids and were examined via transmission electron microscopy. Electron energy loss spectroscopy was employed to characterize the aerosol. A differential mobility analyzer was used to measure the size distribution of the aerosol. The iron particles were typically 40 nm in diameter and often appeared in isolation from the soot aerosol, suggesting that either they were not formed concurrently with the soot or they remained after oxidation of the surrounding soot. Samples collected from within the flame, and downstream of the flame, indicated that the iron may have been present as very small particles comingled with the soot. The iron particles apparently melted and coalesced as they passed through the high temperature flame tip. Crystallization of the iron proceeded as the postflame gases cooled by mixing with external air. The flame system was shown to be capable of consistently producing steady concentrations of soot and iron for delivery to animals, without the confounding presence of toxic gaseous compounds.

A high percentage of neonatal human infants exposed to prolonged assisted ventilation with supplemental oxygen develop airway hyperreactivity. In order to demonstrate that this effect could be replicated in guinea pigs, 4-day-old pups were exposed either to air or 70% oxygen for 4 days. Nine days later each group was subjected to a histamine challenge and differences in respiratory mechanics were determined. The airway pressure response of the hyperoxia group was significantly greater and the respiratory compliance was significantly less than those of the air-exposed pups. The role of inflammation was assessed both by analysis of bronchoalveolar lavage fluid (BAL) and by histopathology on animals 1 day after discontinuation of the exposures. There were no differences between the two groups in BAL protein, total cell count, or the white blood cell (WBC) differential. Histology did not show any evidence of a difference between the two groups in inflammation or in airway remodeling.

Male strain A/J mice were exposed for 6 h/day, 5 days/wk to aged and diluted cigarette sidestream smoke (ADSS) at a chamber concentration of 4 mg/m3 of total suspended particulate matter (TSP). After 6 mo, the lungs were examined for altered expression of cytochrome P-450 isozymes and for differences in total alveolar tissue volume or surface area, as well as changes in the numbers of epithelial type II cells and alveolar macrophages. Morphologic measurements showed no statistically significant differences for the air, alveolar tissue, or capillary volumes of the lungs or changes in the total number of epithelial type II cells or alveolar macrophages. In contrast, cytochrome P-4501A1 was elevated in the lungs of ADSS-exposed animals and localized in capillary endothelial cells. CYP2B1 was present in airway epithelial cells as well as in epithelial cells throughout the lung parenchyma, but its distribution was not changed by ADSS exposure. Isozyme CYP2E1 was also found in airway epithelial cells, b...

Previous studies of the effects of environmental tobacco smoke have used artificial systems for generating aged and diluted sidestream cigarette smoke. Generally these systems have been designed for large chambers, which require expensive smoking machines, use large air flows, and are labor-intensive. We present a new method for producing sidestream smoke and describe an exposure system for smaller chambers that collects, ages, and dilutes smoke to simulate environmentally relevant conditions. Furthermore, our system is relatively inexpensive, maintains consistent levels of total suspended particulates (TSP) and carbon mon-oxide that can be set at a variety of concentrations, and significantly reduces the manual component of exposure studies.

The link between air pollution and adverse pulmonary health effects is well established. The National Ambient Air Quality Standards were formulated to protect human health. These standards are strictly enforced based on strong associations between elevated air pollution levels and increased emergency room visits and hospitalizations due to respiratory conditions. Impacts of air pollution on lung health occur due to the direct interaction between the external environment and internal biological systems and processes. The innate immune system is one of the first lines of defense against inhaled air contaminants and is characterized by activation of key signaling pathways and inflammatory cell recruitment to the lung. Numerous independent and often redundant pathways participate in innate and adaptive immune responses. Given the impact of air pollution on human health, extensive research efforts have aimed to characterize the mechanisms of response to various air pollutants and evaluate risk factors contributing to individual susceptibility. A significant body of evidence exists to document air pollution-induced alterations in proinflammatory or oxidative signaling molecules. However, the role of specific pathways participating in the propagation of the inflammatory effects remains unclear. One hypothesis for interindividual susceptibility to inhaled air pollutants is that genetic polymorphisms in inflammatory or oxidative stress pathways may contribute to the diverse range of the inflammatory response. Activation of numerous receptors associated with airway cells culminates in the translocation of nuclear factor-kappa B and other transcription factors to the nucleus, and therefore initiation of altered signaling of proinflammatory mediators. Alterations in the transcription and expression of inflammatory mediators following exposure to air pollution are well documented. However, the interaction between specific air pollutants and specific cell surface and intracellular receptors has not been clearly defined. Involvement of specific pathways in the innate immune response may be dependent on differential physical and chemical characteristics of air pollution. One pathway implicated in the response to inhaled air pollutants is initiated by the activation of Toll-like receptors (TLRs). TLRs and downstream proinflammatory mediators are well studied for their role in pathogen response, yet gaps in the understanding of TLR response to nonpathogenic agents, such as air pollution, exist. TLRs are associated with inflammation and allergy, and emerging evidence suggests they may also play a role in the response and susceptibility to air pollution. However, the specific component, exogenous or endogenous, responsible for the association between air pollution and TLR activation has yet to be clearly identified. Improved understanding of pulmonary response mechanisms and potential mediators of susceptibility to air pollution, including the role of TLRs, may contribute to a reduction of the health burden of air pollution-induced detriments to lung health. This review provides a background of air pollution, health effects associated with exposure to air pollution, and potential contributors to interindividual variability, with a specific focus on TLRs as potential modulators of the immune response.

Aerosol Science and Technology 39(2): 85–91 We inadvertently failed to recognize the contribution Paul Baron and co-workers, who originally reported the method of mixing the bed material and dust t...