Mechanical Alterations in airway smooth muscle after interaction with indoor pollutant – A mathematical model.

The viscoelasticity of mammalian lung is determined by the mechanical properties and structural regulation of the airway smooth muscle (ASM). The exposure to polluted air may deteriorate these properties with harmful consequences to individual health. Formaldehyde (FA) is an important indoor pollutant found among volatile organic compounds. This pollutant permeates through the smooth muscle tissue forming covalent bonds between proteins in the extracellular matrix and intracellular protein structure changing mechanical properties of ASM and inducing asthma symptoms, such as airway hyperresponsiveness, even at low concentrations. In the experimental scenario, the mechanical effect of FA is the stiffening of the tissue, but the mechanism behind this effect is not fully understood. Thus, the aim of this study is to reproduce the mechanical behavior of the ASM, such as contraction and stretching, under FA action or not. For this, it was created a two-dimensional viscoelastic network model based on Voronoi tessellation solved using Runge-Kutta method of fourth order. The equilibrium configuration was reached when the forces in different parts of the network were equal. This model simulates the mechanical behavior of ASM through of a network of dashpots and springs. This dashpot-spring mechanical coupling mimics the composition of the actomyosin machinery of ASM through the contraction of springs to a minimum length. We hypothesized that formation of covalent bonds, due to the FA action, can be represented in the model by a simple change in the elastic constant of the springs, while the action of methacholine (MCh) reduce the equilibrium length of the spring. A sigmoid curve of tension as a function of MCh doses was obtained, showing increased tension when the muscle strip was exposed to FA. Our simulations suggest that FA, at a concentration of 0.1 ppm, can affect the elastic properties of the smooth muscle ¯bers by a factor of 120%. We also analyze the dynamic mechanical properties, observing the viscous and elastic behavior of the network. Finally, the proposed model, although simple, incorporates the phenomenology of both MCh and FA and reproduces experimental results observed with in vitro exposure of smooth muscle to FA. Thus, this new mechanical approach incorporates several well know features of the contractile system of the cells in a tissue level model. The model can also be used in different biological scales.

Mechanical alterations in airway smooth muscle after interaction with indoor pollutant - A mathematical model

The viscoelasticity of mammalian lung is determined by the mechanical properties and structural regulation of the airway smooth muscle (ASM). The exposure to polluted air may deteriorate these properties with harmful consequences to individual health. Formaldehyde (FA) is an important indoor pollutant found among volatile organic compounds. This pollutant permeates through the smooth muscle tissue forming covalent bonds between proteins in the extracellular matrix and intracellular protein structure changing mechanical properties of ASM and inducing asthma symptoms, such as airway hyperresponsiveness, even at low concentrations. In the experimental scenario, the mechanical effect of FA is the stiffening of the tissue, but the mechanism behind this effect is not fully w1derstood. Thus, the aim of this study is to reproduce the mechanical behavior of the ASM, such as contraction and stretching, under FA action or not. For this, it was created a two-dimensional viscoelastic network model based on Voronoi tessellation solved using Runge-Kutta method of fourth order. The equilibrium configuration was reached when the forces in different parts of the network were equal. This model simulates the mechanical behavior of ASM through of a network of dashpots and springs. This dashpot-spring mechanical coupling mimics the composition of the actomyosin machinery of ASM through the contraction of springs to a minimum length. We hypothesized that formation of covalent bonds, due to the FA action, can be represented in the model by a simple change in the elastic constant of the springs, while the action of methacholinc (MCh) reduce the equilibrium length of the spring. A sigmoid curve of tension as a function of MCh doses was obtained, showing increased tension when the muscle strip was exposed to FA. Our simulations suggest that FA, at a concentration of 0.1 ppm, can affect the elastic properties of the smooth muscle fibers by a factor of 120%. We also analyze the dynamic mechanical properties, observing the viscous and elastic behavior of the network. Finally, the proposed model, although simple, ir1corporates the phenomenology of both MCh and FA and reproduces experirnental results observed with ir1 vitro exposure of smooth muscle to .FA. Thus, this new mechanical approach incorporates several well know features of the contractile system of the cells ir1 a tissue level model. The model can also be used in different biological scales.

Exposure to moderate air pollution during late pregnancy and cord blood cytokine secretion in healthy neonates

Background/Objectives Ambient air pollution can alter cytokine concentrations as shown in vitro and following short-term exposure to high air pollution levels in vivo. Exposure to pollution during late pregnancy has been shown to affect fetal lymphocytic immunophenotypes. However, effects of prenatal exposure to moderate levels of air pollutants on cytokine regulation in cord blood of healthy infants are unknown. Methods In a birth cohort of 265 healthy term-born neonates, we assessed maternal exposure to particles with an aerodynamic diameter of 10 µm or less (PM10), as well as to indoor air pollution during the last trimester, specifically the last 21, 14, 7, 3 and 1 days of pregnancy. As a proxy for traffic-related air pollution, we determined the distance of mothers' homes to major roads. We measured cytokine and chemokine levels (MCP-1, IL-6, IL-10, IL-1ß, TNF-α and GM-CSF) in cord blood serum using LUMINEX technology. Their association with pollution levels was assessed using regression analysis, adjusted for possible confounders. Results Mean (95%-CI) PM10 exposure for the last 7 days of pregnancy was 18.3 (10.3–38.4 µg/m3). PM10 exposure during the last 3 days of pregnancy was significantly associated with reduced IL-10 and during the last 3 months of pregnancy with increased IL-1ß levels in cord blood after adjustment for relevant confounders. Maternal smoking was associated with reduced IL-6 levels. For the other cytokines no association was found. Conclusions Our results suggest that even naturally occurring prenatal exposure to moderate amounts of indoor and outdoor air pollution may lead to changes in cord blood cytokine levels in a population based cohort.

Exposure modeling of high-frequency electromagnetic fields

We developed a geospatial model that calculates ambient high-frequency electromagnetic field (HF-EMF) strengths of stationary transmission installations such as mobile phone base stations and broadcast transmitters with high spatial resolution in the order of 1 m. The model considers the location and transmission patterns of the transmitters, the three-dimensional topography, and shielding effects by buildings. The aim of the present study was to assess the suitability of the model for exposure monitoring and for epidemiological research. We modeled time-averaged HF-EMF strengths for an urban area in the city of Basel as well as for a rural area (Bubendorf). To compare modeling with measurements, we selected 20 outdoor measurement sites in Basel and 18 sites in Bubendorf. We calculated Pearson's correlation coefficients between modeling and measurements. Chance-corrected agreement was evaluated by weighted Cohen's kappa statistics for three exposure categories. Correlation between measurements and modeling of the total HF-EMF strength was 0.67 (95% confidence interval (CI): 0.33-0.86) in the city of Basel and 0.77 (95% CI: 0.46-0.91) in the rural area. In both regions, kappa coefficients between measurements and modeling were 0.63 and 0.77 for the total HF-EMF strengths and for all mobile phone frequency bands. First evaluation of our geospatial model yielded substantial agreement between modeling and measurements. However, before the model can be applied for future epidemiologic research, additional validation studies focusing on indoor values are needed to improve model validity.Journal of Exposure Science and Environmental Epidemiology (2008) 18, 183-191; doi:10.1038/sj.jes.7500575; published online 4 April 2007.

A prediction model for personal radio frequency electromagnetic field exposure

Radio frequency electromagnetic fields (RF-EMF) in our daily life are caused by numerous sources such as fixed site transmitters (e.g. mobile phone base stations) or indoor devices (e.g. cordless phones). The objective of this study was to develop a prediction model which can be used to predict mean RF-EMF exposure from different sources for a large study population in epidemiological research. We collected personal RF-EMF exposure measurements of 166 volunteers from Basel, Switzerland, by means of portable exposure meters, which were carried during one week. For a validation study we repeated exposure measurements of 31 study participants 21 weeks after the measurements of the first week on average. These second measurements were not used for the model development. We used two data sources as exposure predictors: 1) a questionnaire on potentially exposure relevant characteristics and behaviors and 2) modeled RF-EMF from fixed site transmitters (mobile phone base stations, broadcast transmitters) at the participants' place of residence using a geospatial propagation model. Relevant exposure predictors, which were identified by means of multiple regression analysis, were the modeled RF-EMF at the participants' home from the propagation model, housing characteristics, ownership of communication devices (wireless LAN, mobile and cordless phones) and behavioral aspects such as amount of time spent in public transports. The proportion of variance explained (R2) by the final model was 0.52. The analysis of the agreement between calculated and measured RF-EMF showed a sensitivity of 0.56 and a specificity of 0.95 (cut-off: 90th percentile). In the validation study, the sensitivity and specificity of the model were 0.67 and 0.96, respectively. We could demonstrate that it is feasible to model personal RF-EMF exposure. Most importantly, our validation study suggests that the model can be used to assess average exposure over several months.

Prediction of residential radon exposure of the whole Swiss population: comparison of model-based predictions with measurement-based predictions

Radon plays an important role for human exposure to natural sources of ionizing radiation. The aim of this article is to compare two approaches to estimate mean radon exposure in the Swiss population: model-based predictions at individual level and measurement-based predictions based on measurements aggregated at municipality level. A nationwide model was used to predict radon levels in each household and for each individual based on the corresponding tectonic unit, building age, building type, soil texture, degree of urbanization, and floor. Measurement-based predictions were carried out within a health impact assessment on residential radon and lung cancer. Mean measured radon levels were corrected for the average floor distribution and weighted with population size of each municipality. Model-based predictions yielded a mean radon exposure of the Swiss population of 84.1 Bq/m(3) . Measurement-based predictions yielded an average exposure of 78 Bq/m(3) . This study demonstrates that the model- and the measurement-based predictions provided similar results. The advantage of the measurement-based approach is its simplicity, which is sufficient for assessing exposure distribution in a population. The model-based approach allows predicting radon levels at specific sites, which is needed in an epidemiological study, and the results do not depend on how the measurement sites have been selected.

Exposure to the Asp f 1 allergen in nonindustrial occupational environments

Sick Building Syndrome is a prevalent problem with patient complaints similar to typical allergy symptoms. Unlike most household allergens, the Asp f 1 allergen is conceivably ubiquitous in the work environment. This project examined levels of the Asp f 1 allergen in office and non-industrial occupational environments, and studied the bioaerosol and dust reservoirs of Aspergillus fumigatus responsible for those levels. ^ Culturable bioaerosols of total mesophilic fungi were sampled with Andersen N6 impactors. Aggressive airborne and bulk dust samples were concurrently collected and assayed for Asp f 1. Bulk dusts were selectively cultured for A. fumigatus. Samples were collected during both wet and dry climatological conditions to examine the possibility of Asp f 1 increases due to fungal growth blooms. ^ Only very low levels of Asp f 1 were detected in relatively few samples. Analysis of wet versus dry period samples showed no differences in Asp f 1 levels, although A. fumigatus counts from dusts did fluctuate significantly with exterior moisture events as did indoor prevalence of total colony forming units. These results indicate that even in the presence of elevated fungal concentrations, levels of Asp f 1 are extremely low. These levels do not correlate with climatological moisture events, despite distinct fungal blooms in the days immediately following those events. Non-industrial office buildings devoid of indoor air quality issues did not demonstrate significant levels or occurrence of Asp f 1 contamination in the geographical region of this study. ^

Polybrominated diphenyl ethers: Potential human exposure through household dust and dryer lint

This MPH thesis consists of (1) literature review of the relatively new synthetic persistent organic pollutants (POP), polybrominated diphenyl ethers (PBDEs), a type of flame retardant posing a potential public health hazard, (2) Presentation of data on PBDE levels in dryer lint from Dallas, TX and Hamburg, Germany. ^ PBDEs are used as additive fire retardants in plastics, polyurethane foam and electronic equipment to reduce flammability and thus save life and property. PBDEs have been widely used beginning in the 1970s. They resemble polychlorinated biphenyls (PCBs) in structure and toxicity. PBDEs are found in environmental sediments, sludges, and wildlife and even in human blood, milk and tissues. ^ PBDEs, due to their lipophilicity, accumulate in fat and other tissues and biomagnify up the food chain, with increasing concentrations. Animal studies have suggested potential health effects including thyroid disruption, permanent learning and memory impairment, fetal malformations, developmental neurotoxicity and, at high doses, possibly cancer. ^ PBDE levels are increasing in blood and breast milk in North America, but PBDEs intake unlike PCBs appears to be not primarily through food; food PBDE levels in the U.S. are not markedly higher than in Europe yet U.S. human blood and milk levels are much higher. For this reason various exposure pathways including PBDE contaminated dust and air have been studied to better characterize routes of PBDE intake into humans. ^ The scientific literature on PBDE levels in household dust reports higher PBDE concentration in dust than that found in dryer lint; levels in the U.S are elevated compared to other countries with congeners such as BDE 47, 99, 100 and 209 predominating. The United Kingdom has elevated BDE 209 due to high usage of Deca commercial mixture. These studies suggest that indoor PBDE contamination through household dust could be a potential source of PBDE exposure and body burden especially in young children. ^ PBDE levels in dryer lint from U.S ranged from 321 to 3073 ng/g (Mean: 1138 ng/g, Median: 803 ng/g) and from Germany were from 330 to 2069 ng/g (Median: 71ng/g, Mean: 361 ng/g). High median levels in U.S samples indicate contamination of lint with PBDEs although the source of the PBDEs in lint may be from dryer electrical components or air deposition onto clothes, lint may be one source of PBDE exposure to humans. ^

Use of light intensity, temperature, and humidity to verify exposure location

Research studies on the association between exposures to air contaminants and disease frequently use worn dosimeters to measure the concentration of the contaminant of interest. But investigation of exposure determinants requires additional knowledge beyond concentration, i.e., knowledge about personal activity such as whether the exposure occurred in a building or outdoors. Current studies frequently depend upon manual activity logging to record location. This study's purpose was to evaluate the use of a worn data logger recording three environmental parameters—temperature, humidity, and light intensity—as well as time of day, to determine indoor or outdoor location, with an ultimate aim of eliminating the need to manually log location or at least providing a method to verify such logs. For this study, data collection was limited to a single geographical area (Houston, Texas metropolitan area) during a single season (winter) using a HOBO H8 four-channel data logger. Data for development of a Location Model were collected using the logger for deliberate sampling of programmed activities in outdoor, building, and vehicle locations at various times of day. The Model was developed by analyzing the distributions of environmental parameters by location and time to establish a prioritized set of cut points for assessing locations. The final Model consisted of four "processors" that varied these priorities and cut points. Data to evaluate the Model were collected by wearing the logger during "typical days" while maintaining a location log. The Model was tested by feeding the typical day data into each processor and generating assessed locations for each record. These assessed locations were then compared with true locations recorded in the manual log to determine accurate versus erroneous assessments. The utility of each processor was evaluated by calculating overall error rates across all times of day, and calculating individual error rates by time of day. Unfortunately, the error rates were large, such that there would be no benefit in using the Model. Another analysis in which assessed locations were classified as either indoor (including both building and vehicle) or outdoor yielded slightly lower error rates that still precluded any benefit of the Model's use.^

An SAB report : human exposure assessment : a guide to risk ranking, risk reduction, and research planning /

"EPA-SAB-IAQC-95-005."

Occupational exposure to particles during hotel´s rooms cleaning

Background: The majority of studies investigated ambient particles, although in most industrialized countries people spend most of their time indoors and significant emissions of fine and ultrafine particles leading to human exposure are caused by various indoor tasks, including cleaning tasks. Objective: To characterize the occupational exposure to particles during cleaning of hotel's rooms. Methodology: Measurements of mass concentration and particle number concentration were performed before and during cleaning tasks in two rooms with different floor types (wood and carpet) with the equipment Lighthouse, model 3016 IAQ. Results: Considering mass concentration, particles with higher were responsable for higher leves of contamination, particularly PM5.0 and PM10.0. However, considering the particle number concentration, the smaller particle size obtained the higher values. Conclusion: It was observed higher number of particles of the smaller size in all tasks, which is associated with worse health effects. It was observed that the room with wood in the floor has lower values when compared to the room with carpet. The tasks with greater exposure were the 'vacuuming' and 'clean up powder'.

Exposure Assessment for Formaldehyde and Acetaldehyde in the Workplace

Personal exposure and possible cancer risk to formaldehyde and acetaldehyde were appraised in 8 work places at a university in Brazil. Levels of formaldehyde measured ranged from 22.5 to 161.5 g·m 3 and from 18.3 to 91.2 g·m 3 for acetaldehyde. The personal exposure, expressed as the potential dose in indoor air, was calculated to range from 129.8 to 930.4 g·day 1 (low exposure) and 183.9 to 1318.1 g·day 1 (medium exposure) for formaldehyde and 105.5 to 525.3 g·day 1 (low exposure) and 149.5 to 744.2 g·day 1 (medium exposure) for acetaldehyde. The indoor/outdoor ratio showed the existence of indoor sources of the compounds which were mainly in practical classes and research laboratories. The highest formaldehyde and acetaldehyde levels were found where chemical reagents were manipulated. Relating the levels found to the permissible limit given by the US OSHA showed there was no particular risk although some formaldehyde levels did exceed the lower exposure limit of the US agency NIOSH. Any cancer risk would be highest for female technicians and teaching researchers.

Indoor environment and the impact on the health of pre-exisiting asthmatics at work: the development of a risk management framework

This thesis examines the spatial and temporal variation in nitrogen dioxide (NO2) levels in Guernsey and the impacts on pre-existing asthmatics. Whilst air quality in Guernsey is generally good, the levels of NO2 exceed UK standards in several locations. The evidence indicates that people suffering from asthma have exacerbation of their symptoms if exposed to elevated levels of air pollutants including NO2, although this research has never been carried out in Guernsey before. In addition, exposure assessment of individuals is rarely carried out and research in this area is limited due to the complexity of undertaking such a study, which will include a combination of exposures in the home, the workplace and ambient exposures, which vary depending on the individual daily experience. For the first time in Guernsey, this research has examined NO2 levels in correlation with asthma patient admissions to hospital, assessment of NO2 exposures in typical homes and typical workplaces in Guernsey. The data showed a temporal correlation between NO2 levels and the number of hospital admissions and the trend from 2008-2012 was upwards. Statistical analysis of the data did not show a significant linear correlation due to the small size of the data sets. Exposure assessment of individuals showed a spatial variation in exposures in Guernsey and assessment in indoor environments showed that real-time analysis of NO2 levels needs to be undertaken if indoor micro environments for NO2 are the be assessed adequately. There was temporal and spatial variation in NO2 concentrations measured using diffusion tubes, which provide a monthly mean value, and analysers measuring NO2 concentrations in real time. The research shows that building layout and design are important factors for good air flow and ventilation and the dispersion of NO2 indoors. Environmental Health Officers have statutory responsibilities for ambient air quality, hygiene of buildings and workplace environments and this role needs to be co-ordinated with healthcare professionals to improve health outcomes for asthmatics. The outcome of the thesis was the development of a risk management framework for pre-existing asthmatics at work for use by regulators of workplaces and an information leaflet to assist in improving health outcomes for asthmatics in Guernsey.

Human exposure to particulate and gaseous pollutants in a bar.

There is increasing evidence of a causal link between airborne particles and ill health and this study examined the exposure to both airborne particles and the gas phase contaminants of environmental tobacco smoke (ETS) in a bar. The work reported here utilized concurrent and continuous monitoring using real-time optical scattering personal samplers to record particulate (PM10) concentrations at two internal locations. Very high episodes were observed in seating areas compared with the bar area. A photo-acoustic multi-gas analyser was used to record the gas phases (CO and CO2) at eight different locations throughout the bar and showed little spatial variation. This gave a clear indication of the problems associated with achieving acceptable Indoor Air Quality in a public space and identified a fundamental problem with the simplistic design approach taken to ventilate the space. Both gaseous and particulate concentrations within the bar were below maximum recommended levels although the time-series analysis illustrated the highly episodic nature of this exposure.

Comparison of indoor and outdoor fungi and particles in poultry units

A descriptive study was developed in order to compare indoor and outdoor air contamination caused by fungi and particles in seven poultry units. Twenty eight air samples of 25 litters were collected through the impaction method on malt extract agar. Air sampling and particles concentration measurement were done in the interior and also outside premises of the poultries’ pavilions. Regarding the fungal load in the air, indoor concentration of mold was higher than outside air in six poultry units. Twenty eight species / genera of fungi were identified indoor, being Scopulariopsis brevicaulis (40.5%) the most commonly isolated species and Rhizopus sp. (30.0%) the most commonly isolated genus. Concerning outdoor, eighteen species/genera of fungi were isolated, being Scopulariopsis brevicaulis (62.6%) also the most isolated. All the poultry farms analyzed presented indoor fungi different from the ones identified outdoors. Regarding particles’ contamination, PM2.5, PM5.0 and PM10 had a statistically significant difference (Mann-Whitney U test) between the inside and outside of the pavilions, with the inside more contaminated (p=.006; p=.005; p=.005, respectively). The analyzed poultry units are potential reservoirs of substantial amounts of fungi and particles and could therefore free them in the atmospheric air. The developed study showed that indoor air was more contaminated than outdoors, and this can result in emission of potentially pathogenic fungi and particles via aerosols from poultry units to the environment, which may post a considerable risk to public health and contribute to environmental pollution.