Investigating E-Cigarette Particle Emissions and Human Airway Depositions under Various E-Cigarette-Use Conditions.

E-cigarette use is dramatically increasing, particularly with adolescents. While the chemical composition of e-liquids and e-vapor is well characterized, the particle size distribution and the human airways deposition patterns of e-cigarette particles are understudied and poorly understood despite their likely contribution to adverse health effects from e-cigarette usage. In this study, we examined the impacts of e-cigarette device power, e-liquid composition, and vaping topography on e-cigarette particle sizes and their deposition in human airways. In addition, we observed that particle measurement conditions (dilution ratio, temperature, and humidity) significantly affect measured e-cigarette particle sizes. E-cigarette power output significantly increased particle count median diameters (CMD) from 174 ± 13 (particles generated under 6.4 W) to 236 ± 14 nm (particles generated under 31.1 W). E-cigarette particles generated from propylene glycol-based e-liquids (CMD = 145 ± 8 nm and mass median diameter [MMD] = 3.06 ± 0.17 µm) were smaller than those generated from vegetable glycerin-based e-liquids (CMD = 182 ± 9 nm and MMD = 3.37 ± 0.21 µm). Puff volume also impacted vapor particle size: CMD and MMD were 154 ± 11 nm and 3.50 ± 0.27 µm, 163 ± 6 nm and 3.35 ± 0.24 µm, and 146 ± 12 nm and 2.95 ± 0.14 µm, respectively, for 35, 90, and 170 mL puffs. Estimated e-cigarette particle mass deposition fractions in tracheobronchial and bronchoalveolar regions were 0.504-0.541 and 0.073-0.306, respectively. Interestingly, e-cigarette particles are smaller than the particles generated from cigarette smoking but have similar human airway deposition patterns.

Urban airborne particle exposure impairs human lung and blood Mycobacterium tuberculosis immunity.

RATIONALE: Associations between urban (outdoor) airborne particulate matter (PM) exposure and TB and potential biological mechanisms are poorly explored. OBJECTIVES: To examine whether in vivo exposure to urban outdoor PM in Mexico City and in vitro exposure to urban outdoor PM2.5 (< 2.5 µm median aerodynamic diameter) alters human host immune cell responses to Mycobacterium tuberculosis. METHODS: Cellular toxicity (flow cytometry, proliferation assay (MTS assay)), M. tuberculosis and PM2.5 phagocytosis (microscopy), cytokine-producing cells (Enzyme-linked immune absorbent spot (ELISPOT)), and signalling pathway markers (western blot) were examined in bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from healthy, non-smoking, residents of Mexico City (n=35; 13 female, 22 male). In vivo-acquired PM burden in alveolar macrophages (AM) was measured by digital image analysis. MEASUREMENTS AND MAIN RESULTS: In vitro exposure of AM to PM2.5 did not affect M. tuberculosis phagocytosis. High in vivo-acquired AM PM burden reduced constitutive, M. tuberculosis and PM-induced interleukin-1ß production in freshly isolated BAC but not in autologous PBMC while it reduced constitutive production of tumour necrosis factor-alpha in both BAC and PBMC. Further, PM burden was positively correlated with constitutive, PM, M. tuberculosis and purified protein derivative (PPD)-induced interferon gamma (IFN-γ) in BAC, and negatively correlated with PPD-induced IFN-γ in PBMC. CONCLUSIONS: Inhalation exposure to urban air pollution PM impairs important components of the protective human lung and systemic immune response against M. tuberculosis. PM load in AM is correlated with altered M. tuberculosis-induced cytokine production in the lung and systemic compartments. Chronic PM exposure with high constitutive expression of proinflammatory cytokines results in relative cellular unresponsiveness.

Hydroxyl Radicals in E-Cigarette Vapor and E-Vapor Oxidative Potentials under Different Vaping Patterns.

Available studies, while limited in number, suggest that e-cigarette vaping induces oxidative stress, with one potential mechanism being the direct formation of reactive oxygen species (ROS) in e-vapor. In the present studies, we measured the formation of hydroxyl radical (•OH), the most destructive ROS, in e-vapor under a range of vaping patterns (i.e., power settings, solvent concentrations, flavorings). Study results show that increased power output and puff volume correspond with the formation of significantly higher amounts of •OH in e-vapor because of elevated coil temperature and oxygen supply. Vegetable glycerin (VG) e-liquids generated higher •OH levels than propylene glycol (PG) e-liquids, as did flavored e-liquids relative to nonflavored e-liquids. E-vapor in combination with ascorbic acid, which is an abundant biological molecule in human epithelial lining fluid, can also induce •OH formation. The dose of radical per puff associated with e-cigarette vaping was 10-1000 times lower than the reported dose generated by cigarette smoking. However, the daily average •OH dose can be comparable to that from cigarette smoking depending on vaping patterns. Overall, e-cigarette users who use VG-based flavored e-cigarettes at higher power output settings may be at increased risk for •OH exposures and related health consequences such as asthma and chronic obstructive pulmonary disease.

Evaluation of E-Vapor Nicotine and Nicotyrine Concentrations under Various E-Liquid Compositions, Device Settings, and Vaping Topographies.

Nicotine is one of the major components of electronic cigarette (e-cigarette) emissions. Nicotyrine is a product of nicotine dehydrogenation in e-vapor and is a known inhibitor of human cytochrome P450 enzyme, which mediates nicotine metabolism. However, the emission of nicotine and especially nicotyrine from e-cigarettes has not been studied under real-world vaping patterns. This study examined the impact of e-liquid composition, e-cigarette device power output, and vaping topography on nicotine and nicotyrine concentrations under real-world vaping patterns. The amount of nicotine emitted from e-cigarettes vaped at high e-liquid nicotine levels, high device power, and large puff volumes ranged from 0.365 µg/puff to 236 µg/puff and was comparable to the amount of nicotine emitted from regular cigarettes. E-cigarette coil temperatures (200-300 °C) favored the formation of nicotyrine: E-cigarette vaping generated 2- to 63-fold more nicotyrine per unit nicotine emission than conventional cigarette smoking. High nicotyrine emission from e-cigarettes indicates that nicotine metabolism could be potentially interrupted, which could lead to reduced e-cigarette usage, and result in lower exposures to toxic chemicals (e.g., formaldehyde and acetaldehyde). However, higher serum nicotine levels might increase cancer risks by stimulating nicotinic acetylcholine receptors (nAchRs).

Air pollution particulate matter alters antimycobacterial respiratory epithelium innate immunity.

Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 µm (PM2.5) and 10 µm (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human ß-defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB.

Static and Dynamic Microscopy of the Chemical Stability and Aggregation State of Silver Nanowires in Components of Murine Pulmonary Surfactant.

The increase of production volumes of silver nanowires (AgNWs) and of consumer products incorporating them may lead to increased health risks from occupational and public exposures. There is currently limited information about the putative toxicity of AgNWs upon inhalation and incomplete understanding of the properties that control their bioreactivity. The lung lining fluid (LLF), which contains phospholipids and surfactant proteins, represents a first contact site with the respiratory system. In this work, the impact of dipalmitoylphosphatidylcholine (DPPC), Curosurf, and murine LLF on the stability of AgNWs was examined. Both the phospholipid and protein components of the LLF modified the dissolution kinetics of AgNWs, due to the formation of a lipid corona or aggregation of the AgNWs. Moreover, the hydrophilic proteins, but neither the hydrophobic surfactant proteins nor the phospholipids, induced agglomeration of the AgNWs. Finally, the generation of a secondary population of nanosilver was observed and attributed to the reduction of Ag(+) ions by the surface capping of the AgNWs. Our findings highlight that combinations of spatially resolved dynamic and static techniques are required to develop a holistic understanding of which parameters govern AgNW behavior at the point of exposure and to accurately predict their risks on human health and the environment.

Suppression of the NF-κB pathway by diesel exhaust particles impairs human antimycobacterial immunity.

Epidemiological studies suggest that chronic exposure to air pollution increases susceptibility to respiratory infections, including tuberculosis in humans. A possible link between particulate air pollutant exposure and antimycobacterial immunity has not been explored in human primary immune cells. We hypothesized that exposure to diesel exhaust particles (DEP), a major component of urban fine particulate matter, suppresses antimycobacterial human immune effector cell functions by modulating TLR-signaling pathways and NF-κB activation. We show that DEP and H37Ra, an avirulent laboratory strain of Mycobacterium tuberculosis, were both taken up by the same peripheral human blood monocytes. To examine the effects of DEP on M. tuberculosis-induced production of cytokines, PBMC were stimulated with DEP and M. tuberculosis or purified protein derivative. The production of M. tuberculosis and purified protein derivative-induced IFN-γ, TNF-α, IL-1ß, and IL-6 was reduced in a DEP dose-dependent manner. In contrast, the production of anti-inflammatory IL-10 remained unchanged. Furthermore, DEP stimulation prior to M. tuberculosis infection altered the expression of TLR3, -4, -7, and -10 mRNAs and of a subset of M. tuberculosis-induced host genes including inhibition of expression of many NF-κB (e.g., CSF3, IFNG, IFNA, IFNB, IL1A, IL6, and NFKBIA) and IFN regulatory factor (e.g., IFNG, IFNA1, IFNB1, and CXCL10) pathway target genes. We propose that DEP downregulate M. tuberculosis-induced host gene expression via MyD88-dependent (IL6, IL1A, and PTGS2) as well as MyD88-independent (IFNA, IFNB) pathways. Prestimulation of PBMC with DEP suppressed the expression of proinflammatory mediators upon M. tuberculosis infection, inducing a hyporesponsive cellular state. Therefore, DEP alters crucial components of antimycobacterial host immune responses, providing a possible mechanism by which air pollutants alter antimicrobial immunity.

Characterization and Quantification of Vehicular Emissions in Abuja Municipality-Implications for Public Health.

Background: Air pollution from vehicular emission and other sources accounts for over seven million global deaths annually and contributes significantly to environmental degradation, including climate change. Vehicular emission is not prioritized for control in Nigeria, thus undermining public health and the Sustainable Development Goals 3, 11 and 13. This study aims to characterize vehicular emissions in Abuja municipality and quantify exhaust air pollutants of commonly used vehicles. Methodology: Cross-sectional exhaust emissions study of vehicles in Abuja Municipal Area Council. Information on the type and age, fuel type, purchase and use category of 543 vehicles on routine Annual Road Worthiness Test at the Computerized Test Center, Abuja. Exhaust levels of CO, CO2 HCHO and PM10 were measured using hand-held devices. IBM SPSS version 26.0.0.0 (2019) statistical software. Results: Toyota brand comprised 52.5% of the vehicles. Over 80% were older than 10 years; 85.5% preowned and 87.3% used for private purposes. PMS was the dominant fuel used (91.1%). Except PM10, older vehicles emitted higher levels of the measured pollutants than newer ones. The differences were significant for CO and HCHO. Diesel-fueled and commercial vehicles also emitted higher levels of CO, HCHO and PM10 compared to PMS-fueled and private vehicles respectively. Conclusions: Strong regulatory policies that discourage over-aged vehicles; speedy adoption of the ECOWAS guidelines on cleaner fuels and emission limits; and coordinated implementation of effective Inspection & Monitoring programme by relevant government agencies are required to safeguard public health and the environment. We also recommend the introduction of vehicles powered by alternative energy, use of bicycles, designation of one-way traffic and pedestrian zones. Key Message: Reducing the threats to the public's health from vehicular air pollution in Abuja municipality requires strong policy and coordinated monitoring programs for effective control.

Impacts of a nanosized ceria additive on diesel engine emissions of particulate and gaseous pollutants.

Fuel additives incorporating nanosized ceria have been increasingly used in diesel engines as combustion promoters. However, few studies have assessed the impact of these nanotechnology-based additives on pollutant emissions. Here, we systematically compare emission rates of particulate and gaseous pollutants from a single-cylinder, four-cycle diesel engine using fuel mixes containing nanoceria of varying concentrations. The test fuels were made by adding different amounts of a commercial fuel additive Envirox into an ultralow-sulfur diesel fuel at 0 (base fuel), 0.1-, 1-, and 10-fold the manufacturer-recommended concentration of 0.5 mL Envirox per liter of fuel. The addition of Envirox resulted in ceria-concentration-dependent emission reductions of CO2, CO, total particulate mass, formaldehyde, acetaldehyde, acrolein, and several polycyclic aromatic hydrocarbons. These reductions at the manufacturer-recommended doping concentration, however, were accompanied by a substantial increase of certain other air pollutants, specifically the number of ultrafine particles (+32%), NO(x) (+9.3%), and the particle-phase benzo[a]pyrene toxic equivalence quotient (+35%). Increasing fuel ceria concentrations also led to decreases in the size of emitted particles. Given health concerns related to ultrafine particles and NO(x), our findings call for additional studies to further evaluate health risks associated with the use of nanoceria additives in various engines under various operating conditions.

High-resolution analytical electron microscopy reveals cell culture media-induced changes to the chemistry of silver nanowires.

There is a growing concern about the potential adverse effects on human health upon exposure to engineered silver nanomaterials (particles, wires, and plates). However, the majority of studies testing the toxicity of silver nanomaterials have examined nominally "as-synthesized" materials without considering the fate of the materials in biologically relevant fluids. Here, in-house silver nanowires (AgNWs) were prepared by a modified polyol process and were incubated in three cell culture media (DMEM, RPMI-1640, and DCCM-1) to examine the impact of AgNW-medium interactions on the physicochemical properties of the AgNWs. High-resolution analytical transmission electron microscopy revealed that Ag2S crystals form on the surface of AgNWs within 1 h of incubation in DCCM-1. In contrast, the incubation of AgNWs in RPMI-1640 or DMEM did not lead to sulfidation. When the DCCM-1 cell culture medium was separated into its small molecule solutes and salts and protein components, the AgNWs were found to sulfidize in the fraction containing small molecule solutes and salts but not in the fraction containing the protein component of the media. Further investigation showed the AgNWs did not readily sulfidize in the presence of isolated sulfur containing amino acids or proteins, such as cysteine or bovine serum albumin (BSA). The results demonstrate that the AgNWs can be transformed by the media before and during the incubation with cells, and therefore, the effects of cell culture media must be considered in the analysis of toxicity assays. Appropriate media and material controls must be in place to allow accurate predictions about the toxicity and, ultimately, the health risk of this commercially relevant class of nanomaterial.

The stability of silver nanoparticles in a model of pulmonary surfactant.

The growing use of silver nanoparticles (AgNPs) in consumer products has raised concerns about their potential impact on the environment and human health. Whether AgNPs dissolve and release Ag(+) ions, or coarsen to form large aggregates, is critical in determining their potential toxicity. In this work, the stability of AgNPs in dipalmitoylphosphatidylcholine (DPPC), the major component of pulmonary surfactant, was investigated as a function of pH. Spherical, citrate-capped AgNPs with average diameters of 14 ± 1.6 nm (n = 200) were prepared by a chemical bath reduction. The kinetics of Ag(+) ion release was strongly pH-dependent. After 14 days of incubation in sodium perchlorate (NaClO4) or perchloric acid (HClO4) solutions, the total fraction of AgNPs dissolved varied from ∼10% at pH 3, to ∼2% at pH 5, with negligible dissolution at pH 7. A decrease in pH from 7 to 3 also promoted particle aggregation and coarsening. DPPC (100 mg·L(-1)) delayed the release of Ag(+) ions, but did not significantly alter the total amount of Ag(+) released after two weeks. In addition, DPPC improved the dispersion of the AgNPs and inhibited aggregation and coarsening. TEM images revealed that the AgNPs were coated with a DPPC layer serving as a semipermeable layer. Hence, lung lining fluid, particularly DPPC, can modify the aggregation state and kinetics of Ag(+) ion release of inhaled AgNPs in the lung. These observations have important implications for predicting the potential reactivity of AgNPs in the lung and the environment.

Human lung immunity against Mycobacterium tuberculosis: insights into pathogenesis and protection.

The study of human pulmonary immunity against Mycobacterium tuberculosis (M.tb) provides a unique window into the biological interactions between the human host and M.tb within the broncho-alveolar microenvironment, the site of natural infection. Studies of bronchoalveolar cells (BACs) and lung tissue evaluate innate, adaptive, and regulatory immune mechanisms that collectively contribute to immunological protection or its failure. In aerogenically M.tb-exposed healthy persons lung immune responses reflect early host pathogen interactions that may contribute to sterilization, the development of latent M.tb infection, or progression to active disease. Studies in these persons may allow the identification of biomarkers of protective immunity before the initiation of inflammatory and disease-associated immunopathological changes. In healthy close contacts of patients with tuberculosis (TB) and during active pulmonary TB, immune responses are compartmentalized to the lungs and characterized by an exuberant helper T-cell type 1 response, which as suggested by recent evidence is counteracted by local suppressive immune mechanisms. Here we discuss how exploring human lung immunity may provide insights into disease progression and mechanisms of failure of immunological protection at the site of the initial host-pathogen interaction. These findings may also aid in the identification of new biomarkers of protective immunity that are urgently needed for the development of new and the improvement of current TB vaccines, adjuvant immunotherapies, and diagnostic technologies. To facilitate further work in this area, methodological and procedural approaches for bronchoalveolar lavage studies and their limitations are also discussed.

Differential expression of Toll-like receptors on human alveolar macrophages and autologous peripheral monocytes.

BACKGROUND: Toll-like receptors (TLRs) are critical components in the regulation of pulmonary immune responses and the recognition of respiratory pathogens such as Mycobacterium Tuberculosis (M.tb). Through examination of human alveolar macrophages this study attempts to better define the expression profiles of TLR2, TLR4 and TLR9 in the human lung compartment which are as yet still poorly defined. METHODS: Sixteen healthy subjects underwent venipuncture, and eleven subjects underwent additional bronchoalveolar lavage to obtain peripheral blood mononuclear and bronchoalveolar cells, respectively. Surface and intracellular expression of TLRs was assessed by fluorescence-activated cell sorting and qRT-PCR. Cells were stimulated with TLR-specific ligands and cytokine production assessed by ELISA and cytokine bead array. RESULTS: Surface expression of TLR2 was significantly lower on alveolar macrophages than on blood monocytes (1.2 +/- 0.4% vs. 57 +/- 11.1%, relative mean fluorescence intensity [rMFI]: 0.9 +/- 0.1 vs. 3.2 +/- 0.1, p < 0.05). The proportion of TLR4 and TLR9-expressing cells and the rMFIs of TLR4 were comparable between alveolar macrophages and monocytes. The surface expression of TLR9 however, was higher on alveolar macrophages than on monocytes (rMFI, 218.4 +/- 187.3 vs. 4.4 +/- 1.4, p < 0.05) while the intracellular expression of the receptor and the proportion of TLR9 positive cells were similar in both cell types. TLR2, TLR4 and TLR9 mRNA expression was lower in bronchoalveolar cells than in monocytes.Pam3Cys, LPS, and M.tb DNA upregulated TLR2, TLR4 and TLR9 mRNA in both, bronchoalveolar cells and monocytes. Corresponding with the reduced surface and mRNA expression of TLR2, Pam3Cys induced lower production of TNF-alpha, IL-1beta and IL-6 in bronchoalveolar cells than in monocytes. Despite comparable expression of TLR4 on both cell types, LPS induced higher levels of IL-10 in monocytes than in alveolar macrophages. M.tb DNA, the ligand for TLR9, induced similar levels of cytokines in both cell types. CONCLUSION: The TLR expression profile of autologous human alveolar macrophages and monocytes is not identical, therefore perhaps contributing to compartmentalized immune responses in the lungs and systemically. These dissimilarities may have important implications for the design and efficacy evaluation of vaccines with TLR-stimulating adjuvants that target the respiratory tract.

The immunology of tuberculosis: from bench to bedside.

Tuberculosis (TB) is an international public health priority and kills almost two million people annually. TB is out of control in Africa due to increasing poverty and HIV coinfection, and drug-resistant TB threatens to destabilize TB control efforts in several regions of the world. Existing diagnostic tools and therapeutic interventions for TB are suboptimal. Thus, new vaccines, immunotherapeutic interventions and diagnostic tools are urgently required to facilitate TB control efforts. An improved understanding of the immunopathogenesis of TB can facilitate the identification of correlates of immune protection, the design of effective vaccines, the rational selection of immunotherapeutic agents, the evaluation of new drug candidates, and drive the development of new immunodiagnostic tools. Here we review the immunology of TB with a focus on aspects that are clinically and therapeutically relevant. An immunologically orientated approach to tackling TB can only succeed with concurrent efforts to alleviate poverty and reduce the global burden of HIV.

The Impact of Device Settings, Use Patterns, and Flavorings on Carbonyl Emissions from Electronic Cigarettes.

Health impacts of electronic cigarette (e-cigarette) vaping are associated with the harmful chemicals emitted from e-cigarettes such as carbonyls. However, the levels of various carbonyl compounds under real-world vaping conditions have been understudied. This study evaluated the levels of carbonyl compounds (e.g., formaldehyde, acetaldehyde, glyoxal, and diacetyl, etc.) under various device settings (i.e., power output), vaping topographies, and e-liquid compositions (i.e., base liquid, flavor types). The results showed that e-vapor carbonyl levels were the highest under higher power outputs. The propylene glycol (PG)-based e-liquids generated higher formaldehyde and acetaldehyde than vegetable glycerin (VG)-based e-liquids. In addition, fruit flavored e-liquids (i.e., strawberry and dragon fruit) generated higher formaldehyde emissions than mint/menthol and creamy/sweet flavored e-liquids. While single-top coils formed 3.5-fold more formaldehyde per puff than conventional cigarette smoking, bottom coils generated 10-10,000 times less formaldehyde per puff. In general, increases in puff volume and longer puff durations generated significantly higher amounts of formaldehyde. While e-cigarettes emitted much lower levels of carbonyl compounds compared to conventional cigarettes, the presence of several toxic carbonyl compounds in e-cigarette vapor may still pose potential health risks for users without smoking history, including youth. Therefore, the public health administrations need to consider the vaping conditions which generated higher carbonyls, such as higher power output with PG e-liquid, when developing e-cigarette product standards.

Season and size of urban particulate matter differentially affect cytotoxicity and human immune responses to Mycobacterium tuberculosis.

Exposure to air pollution particulate matter (PM) and tuberculosis (TB) are two of the leading global public health challenges affecting low and middle income countries. An estimated 4.26 million premature deaths are attributable to household air pollution and an additional 4.1 million to outdoor air pollution annually. Mycobacterium tuberculosis (M.tb) infects a large proportion of the world's population with the risk for TB development increasing during immunosuppressing conditions. There is strong evidence that such immunosuppressive conditions develop during household air pollution exposure, which increases rates of TB development. Exposure to urban air pollution has been shown to alter the outcome of TB therapy. Here we examined whether in vitro exposure to urban air pollution PM alters human immune responses to M.tb. PM2.5 and PM10 (aerodynamic diameters <2.5µm, <10µm) were collected monthly from rainy, cold-dry and warm-dry seasons in Iztapalapa, a highly populated TB-endemic municipality of Mexico City with elevated outdoor air pollution levels. We evaluated the effects of seasonality and size of PM on cytotoxicity and antimycobacterial host immunity in human peripheral blood mononuclear cells (PBMC) from interferon gamma (IFN-γ) release assay (IGRA)+ and IGRA- healthy study subjects. PM10 from cold-dry and warm-dry seasons induced the highest cytotoxicity in PBMC. With the exception of PM2.5 from the cold-dry season, pre-exposure to all seasonal PM reduced M.tb phagocytosis by PBMC. Furthermore, M.tb-induced IFN-γ production was suppressed in PM2.5 and PM10-pre-exposed PBMC from IGRA+ subjects. This observation coincides with the reduced expression of M.tb-induced T-bet, a transcription factor regulating IFN-γ expression in T cells. Pre-exposure to PM10 compared to PM2.5 led to greater loss of M.tb growth control. Exposure to PM2.5 and PM10 collected in different seasons differentially impairs M.tb-induced human host immunity, suggesting biological mechanisms underlying altered M.tb infection and TB treatment outcomes during air pollution exposures.

Urban Air Pollution Particulates Suppress Human T-Cell Responses to Mycobacterium Tuberculosis.

Tuberculosis (TB) and air pollution both contribute significantly to the global burden of disease. Epidemiological studies show that exposure to household and urban air pollution increase the risk of new infections with Mycobacterium tuberculosis (M.tb) and the development of TB in persons infected with M.tb and alter treatment outcomes. There is increasing evidence that particulate matter (PM) exposure weakens protective antimycobacterial host immunity. Mechanisms by which exposure to urban PM may adversely affect M.tb-specific human T cell functions have not been studied. We, therefore, explored the effects of urban air pollution PM2.5 (aerodynamic diameters ≤2.5µm) on M.tb-specific T cell functions in human peripheral blood mononuclear cells (PBMC). PM2.5 exposure decreased the capacity of PBMC to control the growth of M.tb and the M.tb-induced expression of CD69, an early surface activation marker expressed on CD3+ T cells. PM2.5 exposure also decreased the production of IFN-γ in CD3+, TNF-α in CD3+ and CD14+ M.tb-infected PBMC, and the M.tb-induced expression of T-box transcription factor TBX21 (T-bet). In contrast, PM2.5 exposure increased the expression of anti-inflammatory cytokine IL-10 in CD3+ and CD14+ PBMC. Taken together, PM2.5 exposure of PBMC prior to infection with M.tb impairs critical antimycobacterial T cell immune functions.

Lung Function of Children at Three Sites of Varying Ambient Air Pollution Levels in Uganda: A Cross Sectional Comparative Study.

Air pollution is a major cause of sub-optimal lung function and lung diseases in childhood and adulthood. In this study we compared the lung function (measured by spirometry) of 537 Ugandan children, mean age 11.1 years in sites with high (Kampala and Jinja) and low (Buwenge) ambient air pollution levels, based on the concentrations of particulate matter smaller than 2.5 micrometres in diameter (PM2.5). Factors associated with lung function were explored in a multiple linear regression model. PM2.5 level in Kampala, Jinja and Buwenge were 177.5 µg/m³, 96.3 µg/m³ and 31.4 µg/m³ respectively (p = 0.0000). Respectively mean forced vital capacity as % of predicted (FVC%), forced expiratory volume in one second as % of predicted (FEV1%) and forced expiratory flow 25⁻75% as % of predicted (FEF25⁻75%) of children in high ambient air pollution sites (Kampala and Jinja) vs. those in the low ambient air pollution site (Buwenge subcounty) were: FVC% (101.4%, vs. 104.0%, p = 0.043), FEV1% (93.9% vs. 98.0, p = 0.001) and FEF25⁻75% (87.8 vs. 94.0, p = 0.002). The proportions of children whose %predicted parameters were less than 80% predicted (abnormal) were higher among children living in high ambient air pollution than those living in lower low ambient air pollutions areas with the exception of FVC%; high vs. low: FEV1 < 80%, %predicted (12.0% vs. 5.3%, p = 0.021) and FEF25⁻75 < 80%, %predicted (37.7% vs. 29.3%, p = 0.052) Factors associated with lung function were (coefficient, p-value): FVC% urban residence (-3.87, p = 0.004), current cough (-2.65, p = 0.048), underweight (-6.62, p = 0.000), and overweight (11.15, p = 0.000); FEV1% underweight (-6.54, p = 0.000) and FEF25⁻75% urban residence (-8.67, p = 0.030) and exposure to biomass smoke (-7.48, p = 0.027). Children in study sites with high ambient air pollution had lower lung function than those in sites with low ambient air pollution. Urban residence, underweight, exposure to biomass smoke and cough were associated with lower lung function.

Land use regression models to assess air pollution exposure in Mexico City using finer spatial and temporal input parameters.

The Mexico City Metropolitan Area (MCMA) is one of the largest and most populated urban environments in the world and experiences high air pollution levels. To develop models that estimate pollutant concentrations at fine spatiotemporal scales and provide improved air pollution exposure assessments for health studies in Mexico City. We developed finer spatiotemporal land use regression (LUR) models for PM2.5, PM10, O3, NO2, CO and SO2 using mixed effect models with the Least Absolute Shrinkage and Selection Operator (LASSO). Hourly traffic density was included as a temporal variable besides meteorological and holiday variables. Models of hourly, daily, monthly, 6-monthly and annual averages were developed and evaluated using traditional and novel indices. The developed spatiotemporal LUR models yielded predicted concentrations with good spatial and temporal agreements with measured pollutant levels except for the hourly PM2.5, PM10 and SO2. Most of the LUR models met performance goals based on the standardized indices. LUR models with temporal scales greater than one hour were successfully developed using mixed effect models with LASSO and showed superior model performance compared to earlier LUR models, especially for time scales of a day or longer. The newly developed LUR models will be further refined with ongoing Mexico City air pollution sampling campaigns to improve personal exposure assessments.