Human airway construct model is suitable for studying transcriptome changes associated with indoor air particulate matter toxicity.
ABSTRACT: In vitro models mimicking the human respiratory system are essential when investigating the toxicological effects of inhaled indoor air particulate matter (PM). We present a pulmonary cell culture model for studying indoor air PM toxicity. We exposed normal human bronchial epithelial cells, grown on semi-permeable cell culture membranes, to four doses of indoor air PM in the air-liquid interface. We analyzed the chemokine interleukin-8 concentration from the cell culture medium, protein concentration from the apical wash, measured tissue electrical resistance, and imaged airway constructs using light and transmission electron microscopy. We sequenced RNA using a targeted RNA toxicology panel for 386 genes associated with toxicological responses. PM was collected from a non-complaint residential environment over 1 week. Sample collection was concomitant with monitoring size-segregated PM counts and determination of microbial levels and diversity. PM exposure was not acutely toxic for the cells, and we observed up-regulation of 34 genes and down-regulation of 17 genes when compared to blank sampler control exposure. The five most up-regulated genes were related to immunotoxicity. Despite indications of incomplete cell differentiation, this model enabled the comparison of a toxicological transcriptome associated with indoor air PM exposure.
Project description:There is a need for toxicity tests capable of recognizing indoor environments with compromised air quality, especially in the context of moisture damage. One of the key issues is sampling, which should both provide meaningful material for analyses and fulfill requirements imposed by practitioners using toxicity tests for health risk assessment. We aimed to evaluate different existing methods of sampling indoor particulate matter (PM) to develop a suitable sampling strategy for a toxicological assay. During three sampling campaigns in moisture-damaged and non-damaged school buildings, we evaluated one passive and three active sampling methods: the Settled Dust Box (SDB), the Button Aerosol Sampler, the Harvard Impactor and the National Institute for Occupational Safety and Health (NIOSH) Bioaerosol Cyclone Sampler. Mouse RAW264.7 macrophages were exposed to particle suspensions and cell metabolic activity (CMA), production of nitric oxide (NO) and tumor necrosis factor (TNF?) were determined after 24?h of exposure. The repeatability of the toxicological analyses was very good for all tested sampler types. Variability within the schools was found to be high especially between different classrooms in the moisture-damaged school. Passively collected settled dust and PM collected actively with the NIOSH Sampler (Stage 1) caused a clear response in exposed cells. The results suggested the higher relative immunotoxicological activity of dust from the moisture-damaged school. The NIOSH Sampler is a promising candidate for the collection of size-fractionated PM to be used in toxicity testing. The applicability of such sampling strategy in grading moisture damage severity in buildings needs to be developed further in a larger cohort of buildings.
Project description:Emissions from indoor biomass burning are a major public health concern in developing areas of the world. Less is known about indoor air quality, particularly airborne endotoxin, in homes burning biomass fuel in residential wood stoves in higher income countries. A filter-based sampler was used to evaluate wintertime indoor coarse particulate matter (PM????.?) and airborne endotoxin (EU/m³, EU/mg) concentrations in 50 homes using wood stoves as their primary source of heat in western Montana. We investigated number of residents, number of pets, dampness (humidity), and frequency of wood stove usage as potential predictors of indoor airborne endotoxin concentrations. Two 48-h sampling events per home revealed a mean winter PM????.? concentration (± s.d.) of 12.9 (± 8.6) ?g/m³, while PM?.? concentrations averaged 32.3 (± 32.6) ?g/m³. Endotoxin concentrations measured from PM????.? filter samples were 9.2 (± 12.4) EU/m³ and 1010 (± 1524) EU/mg. PM????.? and PM?.? were significantly correlated in wood stove homes (r = 0.36, P < 0.05). The presence of pets in the homes was associated with PM????.? but not with endotoxin concentrations. Importantly, none of the other measured home characteristics was a strong predictor of airborne endotoxin, including frequency of residential wood stove usage.
Project description:Exposure to air pollution is a leading health risk factor. The variance components and contributions of indoor versus outdoor source determinants of personal exposure to air pollution are poorly understood, especially in settings of household solid fuel use. We conducted a panel study with up to 4 days of repeated measures of integrated gravimetric personal exposure to PM<sub>2.5</sub> and black carbon in 787 men and women (ages 40-79) living in peri-urban villages in northern (Beijing and Shanxi) and southern (Guangxi) China. We simultaneously measured outdoor PM<sub>2.5</sub> and collected questionnaire data on sociodemographic characteristics and indoor pollution sources including tobacco smoking and solid fuel stove use. We obtained over 2000 days of personal exposure monitoring which showed higher exposures in the heating season (geometric mean (GM): 108 versus 65 ?g/m<sup>3</sup> in the non-heating season for PM<sub>2.5</sub>) and among northern participants (GM: 90 versus 59 ?g/m<sup>3</sup> in southern China in the non-heating season for PM<sub>2.5</sub>). We used mixed-effects models to estimate within- and between-participant variance components and to assess the determinants of exposures. Within-participant variance in exposure dominated the total variability (68-95%). Outdoor PM<sub>2.5</sub> was the dominant variable for explaining within-participant variance in exposure to PM<sub>2.5</sub> (16%). Household fuel use (PM<sub>2.5</sub>: 8%; black carbon: 10%) and smoking status (PM<sub>2.5</sub>: 27%; black carbon: 5%) explained the most between-participant variance. Indoor sources (solid fuel stoves, tobacco smoking) were associated with 13-30% higher exposures to air pollution and each 10 ?g/m<sup>3</sup> increase in outdoor PM<sub>2.5</sub> was associated with 6-8% higher exposure. Our findings indicate that repeated measurements of daily exposure are likely needed to capture longer-term exposures in settings of household solid fuel use, even within a single season, and that reducing air pollution from both outdoor and indoor sources is likely needed to achieve measurable reductions in exposures to air pollution.
Project description:INTRODUCTION:Smoke-free air laws have been implemented in many Kentucky communities to protect the public from the harmful effects of secondhand smoke exposure. The impact of different strengths of smoke-free air laws on indoor air quality was assessed. METHODS:Indoor air quality in hospitality venues was assessed in seven communities before and after comprehensive smoke-free air laws and in two communities only after partial smoke-free air laws. One community was measured three times: before any smoke-free air law, after the initial partial law, and after the law was strengthened to cover all workplaces and public places with few exemptions. Real-time measurements of particulate matters with 2.5 mum aerodynamic diameter or smaller (PM(2.5)) were obtained. RESULTS:When comprehensive smoke-free air laws were implemented, indoor PM(2.5) concentrations decreased significantly from 161 to 20 microg/m3. In one community that implemented a comprehensive smoke-free law after initially passing a partial law, indoor PM(2.5) concentrations were 304 microg/m3 before the law, 338 microg/m3 after the partial law, and 9 microg/m3 after the comprehensive law. DISCUSSION:The study clearly demonstrated that partial smoke-free air laws do not improve indoor air quality. A significant linear trend indicated that PM(2.5) levels in the establishments decreased with fewer numbers of burning cigarettes. Only comprehensive smoke-free air laws are effective in reducing indoor air pollution from secondhand tobacco smoke.
Project description:Polyurethane Flexible Foams (PUF) are versatile materials used in upholstered furniture and bed mattresses. Due to the production procedure, fresh foams emit volatile organic compounds (VOC) which may contribute to indoor air exposure. To evaluate the risk for consumers, the VOC concentration measured in chamber tests can be matched against existing benchmarks for indoor air like “Richtwerte” (RW) of the German UBA (Umweltbundesamt), “Lowest Concentration of Interest” (LCI) for construction products or derived no effect levels (DNEL) for consumer inhalation exposure. In a previous paper a method for the derivation of Indoor Air Guidance Values (IAGV) for VOC without RW, LCI or DNEL was developed. The method described made use of a sufficient toxicological database. For substances with an insufficient database, read across to structural analogues is a way forward to estimate Indoor Air Guidance Values (IAGV). In this work a read across exercise, supported by an open source physiology based toxicokinetic (PBTK) modelling program is demonstrated. The use of enzyme kinetic data for phase I and phase II metabolism is discussed and areas for further work were identified. For two substances with very limited toxicological data, allyloxypropanol (isomer mixture of 1-allyloxy-2-propanol and 2-allyloxy-1-propanol) and 2,3-di-ethyl-2,3-dimethylsuccinodintrile, Tentative Indoor Air Guidance Values of 750 µg/m³ and 65 µg/m³ were derived.
Project description:Exposure to specific airborne bacteria indoors is linked to infectious and noninfectious adverse health outcomes. However, the sources and origins of bacteria suspended in indoor air are not well understood. This study presents evidence for elevated concentrations of indoor airborne bacteria due to human occupancy, and investigates the sources of these bacteria. Samples were collected in a university classroom while occupied and when vacant. The total particle mass concentration, bacterial genome concentration, and bacterial phylogenetic populations were characterized in indoor, outdoor, and ventilation duct supply air, as well as in the dust of ventilation system filters and in floor dust. Occupancy increased the total aerosol mass and bacterial genome concentration in indoor air PM(10) and PM(2.5) size fractions, with an increase of nearly two orders of magnitude in airborne bacterial genome concentration in PM(10). On a per mass basis, floor dust was enriched in bacterial genomes compared to airborne particles. Quantitative comparisons between bacterial populations in indoor air and potential sources suggest that resuspended floor dust is an important contributor to bacterial aerosol populations during occupancy. Experiments that controlled for resuspension from the floor implies that direct human shedding may also significantly impact the concentration of indoor airborne particles. The high content of bacteria specific to the skin, nostrils, and hair of humans found in indoor air and in floor dust indicates that floors are an important reservoir of human-associated bacteria, and that the direct particle shedding of desquamated skin cells and their subsequent resuspension strongly influenced the airborne bacteria population structure in this human-occupied environment. Inhalation exposure to microbes shed by other current or previous human occupants may occur in communal indoor environments.
Project description:OBJECTIVES:Ambient particulate matter (PM) is regulated with science-based air quality standards, whereas carcinogens are regulated with a number of "acceptable" cases. Given that PM is also carcinogenic, we identify differences between approaches. METHODS:We assessed the lung cancer deaths for Switzerland attributable to exposure to PM up to 10 µm (PM10) and to five particle-bound carcinogens. For PM10, we used an epidemiological approach based on relative risks with four exposure scenarios compared to two counterfactual concentrations. For carcinogens, we used a toxicological approach based on unit risks with four exposure scenarios. RESULTS:The lung cancer burden using concentrations from 2010 was 10-14 times larger for PM10 than for the five carcinogens. However, the burden depends on the underlying exposure scenarios, counterfactual concentrations and number of carcinogens. All scenarios of the toxicological approach for five carcinogens result in a lower burden than the epidemiological approach for PM10. CONCLUSIONS:Air quality standards-promoted so far by the WHO Air Quality Guidelines-provide a more appealing framework to guide health risk-oriented clean air policymaking than frameworks based on a number of "acceptable" cases.
Project description:BACKGROUND:Air pollution is a leading cause of global disease burden. Lack of suitable methods for long term measuring exposure level at individual level is crippling environmental epidemiology research of air pollution. METHODS:We report an integrative system, Bio3Air, for long term measurement of individual level air pollution exposure, currently focusing on ambient particulate matter (PM). The novel system in real-time quantifies individual's outdoor/indoor status, geological location, lung ventilation rate and PM concentration of individual's surrounding environment, and these metrics are subsequently incorporated in calculating PM exposure. RESULTS:The system is fully developed and tested in China, USA and Canada, and has been successfully applied in epidemiology study. Bio3Air offers high reliability, sensitivity, reproducibility (>99%) and accuracy. It has high time- and spatial- resolution (? 2?min and ? 20?m, respectively). Bio3Air achieved 91.89% consistency with "gold-standard" method (membrane collection and off-line analysis). CONCLUSIONS:Bio3Air represents a substantial methodological advance in environmental health research of air pollution. It captures information relevant in measuring individual's PM exposure (e.g. real-time outdoor/indoor status, location and lung ventilation rate). Such information is typically missed by conventional approaches. Additional features of Bio3Air include easy-to-use, cost-effectiveness and automated data collection, making it a powerful tool facilitating studies of air pollution exposure and health consequences.
Project description:Microbiota associated with airborne particulate matter (PM) is an important indicator of indoor pollution as they can be pathogenic and cause serious health threats to the exposed occupants. Present study aimed to investigate the level of culturable microbes associated with PM and their toxicological characterization in urban and rural houses of Pune city. Highest concentration of bacterial aerosols observed to be associated with PM10 size fraction in urban site (2136 ± 285 CFU/m3) whereas maximum fungal concentration has been measured in rural houses (1521 ± 302 CFU/m3). Predominantly found bacterial species were Bacillus sp., S. aureus, and Pseudomonas aeruginosa and fungal species were Aspergillus sp., Cladosporium sp., and Penicillium sp. in both urban and rural residential premises. Concentration of endotoxin measured using the kinetic Limulus Amebocyte Lysate assay exhibited that the level of endotoxin in both urban and rural sites are associated with household characteristics and the activities performed in indoor as well as outdoor. Cell free DTT assay confirmed the ability of these airborne microbes to induce the production of reactive oxygen species (ROS) varying along with the types of microorganisms. On exposure of A549 cells to airborne microbes, a significant decrease in cell viability was observed in terms of both necrosis and apoptosis pathway. Elevated production of nitric oxide (NO) and proinflammatory cytokines in epithelial cells and macrophages clearly suggest the inflammatory nature of these airborne microbes. Results derived from the present study demonstrated that the indoor air of urban and rural houses of Pune is contaminated in terms of microbial load. Therefore, attention should be paid to control the factors favoring the microbial growth in order to safeguard the health of exposed inhabitants.
Project description:This paper assesses the effect of short-term exposure to particulate matter (PM) air pollution on human cognitive performance via a double cross over experimental design. Two distinct experiments were performed, both of which exposed subjects to low and high concentrations of PM. Firstly, subjects completed a series of cognitive tests after being exposed to low ambient indoor PM concentrations and elevated PM concentrations generated via candle burning, which is a well-known source of PM. Secondly, a different cohort underwent cognitive tests after being exposed to low ambient indoor PM concentrations and elevated ambient outdoor PM concentrations via commuting on or next to roads. Three tests were used to assess cognitive performance: Mini-Mental State Examination (MMSE), the Stroop Color and Word test, and Ruff 2 & 7 test. The results from the MMSE test showed a statistically robust decline in cognitive function after exposure to both the candle burning and outdoor commuting compared to ambient indoor conditions. The similarity in the results between the two experiments suggests that PM exposure is the cause of the short-term cognitive decline observed in both. The outdoor commuting experiment also showed a statistically significant short-term cognitive decline in automatic detection speed from the Ruff 2 and 7 selective attention test. The other cognitive tests, for both the candle and commuting experiments, showed no statistically significant difference between the high and low PM exposure conditions. The findings from this study are potentially far reaching; they suggest that elevated PM pollution levels significantly affect short term cognition. This implies average human cognitive ability will vary from city to city and country to country as a function of PM air pollution exposure.