Biomaterials for Bioprinting Microvasculature.

Microvasculature functions at the tissue and cell level, regulating local mass exchange of oxygen and nutrient-rich blood. While there has been considerable success in the biofabrication of large- and small-vessel replacements, functional microvasculature has been particularly challenging to engineer due to its size and complexity. Recently, three-dimensional bioprinting has expanded the possibilities of fabricating sophisticated microvascular systems by enabling precise spatiotemporal placement of cells and biomaterials based on computer-aided design. However, there are still significant challenges facing the development of printable biomaterials that promote robust formation and controlled 3D organization of microvascular networks. This review provides a thorough examination and critical evaluation of contemporary biomaterials and their specific roles in bioprinting microvasculature. We first provide an overview of bioprinting methods and techniques that enable the fabrication of microvessels. We then offer an in-depth critical analysis on the use of hydrogel bioinks for printing microvascularized constructs within the framework of current bioprinting modalities. We end with a review of recent applications of bioprinted microvasculature for disease modeling, drug testing, and tissue engineering, and conclude with an outlook on the challenges facing the evolution of biomaterials design for bioprinting microvasculature with physiological complexity.

Wearable Spectroradiometer for Dosimetry.

Available wearable dosimeters suffer from spectral mismatch during the measurement of broadband UV and visible radiation in environments that receive radiation from multiple sources emitting differing spectra. We observed this type of multi-spectra environment in all five Washington State cannabis farms visited during a field study investigating worker exposure to ultraviolet radiation in 2018. Spectroradiometers do not suffer from spectral mismatch in these environments, however, an extensive literature review conducted at the time of writing did not identify any spectroradiometers that were directly deployable as wearable dosimetry devices. To close this research gap, we developed a microcontroller system and platform that allows for researchers to mount and deploy the Ocean Insight Flame-S Spectroradiometer as a wearable device for measurement of UV and visible wavelengths (300 to 700 nm). The platform validation consisted of comparing measurements taken under platform control with measurements taken with the spectrometer controlled by a personal computer running the software provided by the spectroradiometer manufacturer. Three Mann-Whitney U-Tests (two-tailed, 95% CI), one for each intensity condition, compared the central tendency between the total spectral power (TSP), the integral of a spectrum measurement, measured under both control schemas. An additional analysis of per pixel agreement and overall platform stability was performed. The three Mann-Whitney tests returned no significant difference between the set of TSPs for each filter condition. These results suggest that the spectroradiometer takes measurements of equivalent accuracy under both control schemas, and can be deployed as a wearable device for the measurement of wavelength resolved UV and visible radiation.

Engineering a Chemically Defined Hydrogel Bioink for Direct Bioprinting of Microvasculature.

Vascularizing printed tissues is a critical challenge in bioprinting. While protein-based hydrogel bioinks have been successfully used to bioprint microvasculature, their compositions are ill-defined and subject to batch variation. Few studies have focused on engineering proangiogenic bioinks with defined properties to direct endogenous microvascular network formation after printing. Here, a peptide-functionalized alginate hydrogel bioink with defined mechanical, rheological, and biochemical properties is developed for direct bioprinting of microvascularized tissues. An integrin-binding peptide (RGD) and a vascular endothelial growth factor-mimetic peptide with a protease-sensitive linker are conjugated onto a biodegradable alginate to synergistically promote vascular morphogenesis and capillary-scale endothelial tube formation. Partial ionic crosslinking before printing converts the otherwise unprintable hydrogel into a viscoelastic bioink with excellent printability and cytocompatibility. We use the bioink to fabricate a compartmentalized vascularized tissue construct, wherein we observe pericyte-endothelial cell colocalization and angiogenic sprouting across a tissue interface, accompanied by deposition of fibronectin and collagen in vascular and tissue components, respectively. This study provides a tunable and translational "off-the-shelf" hydrogel bioink with defined composition for vascularized bioprinting.

Distinct Ultrafine Particle Profiles Associated with Aircraft and Roadway Traffic.

The Mobile ObserVations of Ultrafine Particles study was a two-year project to analyze potential air quality impacts of ultrafine particles (UFPs) from aircraft traffic for communities near an international airport. The study assessed UFP concentrations within 10 miles of the airport in the directions of aircraft flight. Over the course of four seasons, this study conducted a mobile sampling scheme to collect time-resolved measures of UFP, CO2, and black carbon (BC) concentrations, as well as UFP size distributions. Primary findings were that UFPs were associated with both roadway traffic and aircraft sources, with the highest UFP counts found on the major roadway (I-5). Total concentrations of UFPs alone (10-1000 nm) did not distinguish roadway and aircraft features. However, key differences existed in the particle size distribution and the black carbon concentration for roadway and aircraft features. These differences can help distinguish between the spatial impact of roadway traffic and aircraft UFP emissions using a combination of mobile monitoring and standard statistical methods.

Examining the role of wind in human illness due to pesticide drift in Washington state, 2000-2015.

BACKGROUND: Pesticides play an important role in protecting the food supply and the public's health from pests and diseases. By their nature, pesticides can be toxic to unintended target organisms. Changing winds contribute to pesticide drift- the off-target movement of pesticides-and can result in occupational and bystander illness. METHODS: We systematically linked historical weather data to documented pesticide drift illnesses. We used Washington State Department of Health data to identify 252 drift events that included 690 confirmed cases of illness from 2000 to 2015. To characterize wind speed and direction at the time of the events, we paired these data with meteorological data from a network of 171 state weather stations. We report descriptive statistics and the spatio-temporal extent of drift events and compare applicator-reported weather conditions to those from nearby meteorological stations. RESULTS: Most drift events occurred in tree fruit (151/252 = 60%). Ground spraying and aerial applications accounted for 68% and 23% of events, respectively; 69% of confirmed cases were workers, and 31% were bystanders. Confirmed cases were highest in 2014 (129) from 22 events. Complete applicator spray records were available for 57 drift events (23%). Average applicator-reported wind speeds were about 0.9 m •sec- 1 (2 mi •hr- 1) lower than corresponding speeds from the nearest weather station values. CONCLUSIONS: Drift events result from a complex array of factors in the agricultural setting. We used known spatio-temporal aspects of drift and historical weather data to characterize these events, but additional research is needed to put our findings into practice. Particularly critical for this analysis is more accurate and complete information about location, time, wind speed, and wind direction. Our findings can be incorporated into new training materials to improve the practice of pesticide application and for better documentation of spray drift events. A precision agriculture approach offers technological solutions that simplify the task of tracking pesticide spraying and weather conditions. Public health investigators will benefit from improved meteorological data and accurate application records. Growers, applicators, and surrounding communities will also benefit from the explanatory and predictive potential of wind ramping studies.

Using Vehicles' Rendezvous for In Situ Calibration of Instruments in Fleet Vehicle-Based Air Pollution Mobile Monitoring.

This study examines the feasibility of the in situ calibration of instruments for fleet vehicle-based mobile monitoring of ultrafine particles (UFPs) and black carbon (BC) by comparing rendezvous vehicle measurements. Two vehicles with identical makes and models of UFP and BC monitors as well as GPS receivers were sampled within 140 m of each other for 2 h in total during winter in Seattle, Washington. To identify an optimal intervehicle distance for rendezvous calibration, 6 different buffers within 0-140 m for UFP monitors and 5 different buffers within 0-90 m for BC monitors were chosen, and the results of calibration were compared against a reference scenario, which consisted of mobile colocation measurements with both sets of the UFP and BC monitors deployed in one of the vehicles. Results indicate that the optimal distances for rendezvous calibration are 10-80 m for UFP monitors and 0-30 m for BC monitors. In comparison with the mobile colocation calibration, the rendezvous calibration shows a normalized root mean squared deviation of 6-14% and a normalized mean absolute deviation of 4-8% for these monitors. Criteria for applying a rendezvous calibration approach are presented, and an extension of this approach to an instrumented fleet of mobile monitoring vehicles is discussed.

Use of benchmark dose models in risk assessment for occupational handlers of eight pesticides used in pome fruit production.

The benchmark dose has been frequently recommended for the creation of points of departure for regulatory dose limits, but many regulations, including pesticide risk assessment and registration in the United States, continues to rely on NOAEL methods as the OECD toxicological standard methods recommend. This study used data from studies in support of pesticide registration for eight different compounds to build dose-response models and calculate benchmark doses and confidence limits. The results were compared to the NOAEL of the same study. A probabilistic estimate of dose was compared with all points of departure to demonstrate differences in the protective ability of each different selected limit. While neither the BMD/BMDL nor the NOAEL was consistently more protective, the advantage of using the BMD in quantifying the uncertainty of the point of departure is highlighted, and the feasibility of using current OECD-guideline studies for derivation of a BMD is demonstrated in these cases.

Mobile and Fixed-Site Measurements To Identify Spatial Distributions of Traffic-Related Pollution Sources in Los Angeles.

Mobile monitoring and fixed-site monitoring using passive sampling devices (PSD) are popular air pollutant measurement techniques with complementary strengths and weaknesses. This study investigates the utility of combining data from concurrent 2-week mobile monitoring and fixed-site PSD campaigns in Los Angeles in the summer and early spring to identify sources of traffic-related air pollutants (TRAP) and their spatial distributions. There were strong to moderate correlations between mobile and fixed-site PSD measurements of both NO2 and NO x in the summer and spring (Pearson's r between 0.43 and 0.79), suggesting that the two data sets can be reliably combined for source apportionment. PCA identified the major TRAP sources as light-duty vehicle emissions, diesel exhaust, crankcase vent emissions, and an independent source of combustion-derived ultrafine particle emissions. The component scores of those four sources at each site were significantly correlated across the two seasons (Pearson's r between 0.58 and 0.79). Spatial maps of absolute principal component scores showed all sources to be most prominent near major roadways and the central business district and the ultrafine particle source being, in addition, more prominent near the airport. Mobile monitoring combined with fixed-site PSD sampling can provide high spatial resolution estimates of TRAP and can reveal underlying sources of exposure variability.

Comparative Probabilistic Assessment of Occupational Pesticide Exposures Based on Regulatory Assessments.

Implementation of probabilistic analyses in exposure assessment can provide valuable insight into the risks of those at the extremes of population distributions, including more vulnerable or sensitive subgroups. Incorporation of these analyses into current regulatory methods for occupational pesticide exposure is enabled by the exposure data sets and associated data currently used in the risk assessment approach of the Environmental Protection Agency (EPA). Monte Carlo simulations were performed on exposure measurements from the Agricultural Handler Exposure Database and the Pesticide Handler Exposure Database along with data from the Exposure Factors Handbook and other sources to calculate exposure rates for three different neurotoxic compounds (azinphos methyl, acetamiprid, emamectin benzoate) across four pesticide-handling scenarios. Probabilistic estimates of doses were compared with the no observable effect levels used in the EPA occupational risk assessments. Some percentage of workers were predicted to exceed the level of concern for all three compounds: 54% for azinphos methyl, 5% for acetamiprid, and 20% for emamectin benzoate. This finding has implications for pesticide risk assessment and offers an alternative procedure that may be more protective of those at the extremes of exposure than the current approach.

Therapeutic Engineered Hydrogel Coatings Attenuate the Foreign Body Response in Submuscular Implants.

BACKGROUND: Biomedical devices are implanted into mammalian soft tissues to improve, monitor, or restore form or function. The utility of these implants is limited by the subsequent foreign body response (FBR), beginning with inflammation and terminating in a collagen envelope around the device, known as the capsule. This capsule then can contract and distort the shape of the device or limit its effectiveness in interacting with the surrounding host tissues. In the current study, we investigated the effect of therapeutic collagen-coated silicone discs in a rat model of the FBR. METHODS: A 3-dimensional printed mold was used to fabricate collagen-coated silicone discs incorporating 3 therapeutic agents: colchicine, a function-blocking antibody against interleukin 8 (IL-8) receptor B, and a powerful anti-inflammatory steroid, dexamethasone. Discs were implanted submuscularly into a well-characterized rat model of the FBR and evaluated for inflammatory response, fibrotic development, and cytokine release. RESULTS: Coated silicone discs exhibited reduced collagen deposition and little to no foreign body giant cells at the host-silicone interface when compared with the silicone-only group. Therapeutic hydrogels demonstrate a significant decrease in cellular infiltration into the coatings over the 2-week time point in contrast to therapeutic-free hydrogel coatings. Cytokine analysis revealed significant differences between therapeutic-free and therapeutic-containing coatings when compared with silicone-only controls. Levels of IL-1ß, IL-6, monocyte chemotactic protein 1, and macrophage inflammatory protein 3α were affected 48 hours after implantation, while differences in IL-18, growth-regulated oncogene/keratinocyte chemoattractant, and macrophage inflammatory protein 3α were observed 1 week after implantation. CONCLUSIONS: By utilizing the host's innate immune response, our engineered hydrogel coatings delivered therapeutic moieties directly to the implant microenvironment, thus delaying the FBR up to 2 weeks.

Mechanism of action of the anti-inflammatory connexin43 mimetic peptide JM2.

Connexin-based therapeutics have shown the potential for therapeutic efficacy in improving wound healing. Our previous work demonstrated that the connexin43 (Cx43) mimetic peptide juxtamembrane 2 (JM2) reduced the acute inflammatory response to a submuscular implant model by inhibiting purinergic signaling. Given the prospective application in improving tissue-engineered construct tolerance that these results indicated, we sought to determine the mechanism of action for JM2 in the present study. Using confocal microscopy, a gap-FRAP cell communication assay, and an ethidium bromide uptake assay of hemichannel function we found that the peptide reduced cell surface Cx43 levels, Cx43 gap junction (GJ) size, GJ communication, and hemichannel activity. JM2 is based on the sequence of the Cx43 microtubule binding domain, and microtubules have a confirmed role in intracellular trafficking of Cx43 vesicles. Therefore, we tested the effect of JM2 on Cx43-microtubule interaction and microtubule polymerization. We found that JM2 enhanced Cx43-microtubule interaction and that microtubule polymerization was significantly enhanced. Taken together, these data suggest that JM2 inhibits trafficking of Cx43 to the cell surface by promoting irrelevant microtubule polymerization and thereby reduces the number of hemichannels in the plasma membrane available to participate in proinflammatory purinergic signaling. Importantly, this work indicates that JM2 may have therapeutic value in the treatment of proliferative diseases such as cancer. We conclude that the targeted action of JM2 on Cx43 channels may improve the tolerance of implanted tissue-engineered constructs against the innate inflammatory response.

Ambient Air Quality Measurements from a Continuously Moving Mobile Platform: Estimation of Area-Wide, Fuel-Based, Mobile Source Emission Factors Using Absolute Principal Component Scores.

We have applied the absolute principal component scores (APCS) receptor model to on-road, background-adjusted measurements of NOx, CO, CO2, black carbon (BC), and particle number (PN) obtained from a continuously moving platform deployed over nine afternoon sampling periods in Seattle, WA. Two Varimax-rotated principal component features described 75% of the overall variance of the observations. A heavy-duty vehicle feature was correlated with black carbon and particle number, whereas a light-duty feature was correlated with CO and CO2. NOx had moderate correlation with both features. The bootstrapped APCS model predictions were used to estimate area-wide, average fuel-based emission factors and their respective 95% confidence limits. The average emission factors for NOx, CO, BC and PN (14.8, 18.9, 0.40 g/kg, and 4.3×1015 particles/kg for heavy duty vehicles, and 3.2, 22.4, 0.016 g/kg, and 0.19×1015 particles/kg for light-duty vehicles, respectively) are consistent with previous estimates based on remote sensing, vehicle chase studies, and recent dynamometer tests. Information on the spatial distribution of the concentrations contributed by these two vehicle categories relative to background during the sampling period was also obtained.

Design and Fabrication of a Three-Dimensional In Vitro System for Modeling Vascular Stenosis.

Vascular stenosis, the abnormal narrowing of blood vessels, arises from defective developmental processes or atherosclerosis-related adult pathologies. Stenosis triggers a series of adaptive cellular responses that induces adverse remodeling, which can progress to partial or complete vessel occlusion with numerous fatal outcomes. Despite its severity, the cellular interactions and biophysical cues that regulate this pathological progression are poorly understood. Here, we report the design and fabrication of a three-dimensional (3D) in vitro system to model vascular stenosis so that specific cellular interactions and responses to hemodynamic stimuli can be investigated. Tubular cellularized constructs (cytotubes) were produced, using a collagen casting system, to generate a stenotic arterial model. Fabrication methods were developed to create cytotubes containing co-cultured vascular cells, where cell viability, distribution, morphology, and contraction were examined. Fibroblasts, bone marrow primary cells, smooth muscle cells (SMCs), and endothelial cells (ECs) remained viable during culture and developed location- and time-dependent morphologies. We found cytotube contraction to depend on cellular composition, where SMC-EC co-cultures adopted intermediate contractile phenotypes between SMC- and EC-only cytotubes. Our fabrication approach and the resulting artery model can serve as an in vitro 3D culture system to investigate vascular pathogenesis and promote the tissue engineering field.

Impacts of extreme heat on emergency medical service calls in King County, Washington, 2007-2012: relative risk and time series analyses of basic and advanced life support.

BACKGROUND: Exposure to excessive heat kills more people than any other weather-related phenomenon, aggravates chronic diseases, and causes direct heat illness. Strong associations between extreme heat and health have been identified through increased mortality and hospitalizations and there is growing evidence demonstrating increased emergency department visits and demand for emergency medical services (EMS). The purpose of this study is to build on an existing regional assessment of mortality and hospitalizations by analyzing EMS demand associated with extreme heat, using calls as a health metric, in King County, Washington (WA), for a 6-year period. METHODS: Relative-risk and time series analyses were used to characterize the association between heat and EMS calls for May 1 through September 30 of each year for 2007-2012. Two EMS categories, basic life support (BLS) and advanced life support (ALS), were analyzed for the effects of heat on health outcomes and transportation volume, stratified by age. Extreme heat was model-derived as the 95th (29.7 °C) and 99th (36.7 °C) percentile of average county-wide maximum daily humidex for BLS and ALS calls respectively. RESULTS: Relative-risk analyses revealed an 8 % (95 % CI: 6-9 %) increase in BLS calls, and a 14 % (95 % CI: 9-20 %) increase in ALS calls, on a heat day (29.7 and 36.7 °C humidex, respectively) versus a non-heat day for all ages, all causes. Time series analyses found a 6.6 % increase in BLS calls, and a 3.8 % increase in ALS calls, per unit-humidex increase above the optimum threshold, 40.7 and 39.7 °C humidex respectively. Increases in "no" and "any" transportation were found in both relative risk and time series analyses. Analysis by age category identified significant results for all age groups, with the 15-44 and 45-64 year old age groups showing some of the highest and most frequent increases across health conditions. Multiple specific health conditions were associated with increased risk of an EMS call including abdominal/genito-urinary, alcohol/drug, anaphylaxis/allergy, cardiovascular, metabolic/endocrine, diabetes, neurological, heat illness and dehydration, and psychological conditions. CONCLUSIONS: Extreme heat increases the risk of EMS calls in King County, WA, with effects demonstrated in relatively younger populations and more health conditions than those identified in previous analyses.

Ultrafine particle size as a tracer for aircraft turbine emissions.

Ultrafine particle number (UFPN) and size distributions, black carbon, and nitrogen dioxide concentrations were measured downwind of two of the busiest airports in the world, Los Angeles International Airport (LAX) and Hartsfield-Jackson International Airport (ATL - Atlanta, GA) using a mobile monitoring platform. Transects were located between 5 km and 10 km from the ATL and LAX airports. In addition, measurements were taken at 43 additional urban neighborhood locations in each city and on freeways. We found a 3-5 fold increase in UFPN concentrations in transects under the landing approach path to both airports relative to surrounding urban areas with similar ground traffic characteristics. The latter UFPN concentrations measured were distinct in size distributional properties from both freeways and across urban neighborhoods, clearly indicating different sources. Elevated concentrations of Black Carbon (BC) and NO2 were also observed on airport transects, and the corresponding pattern of elevated BC was consistent with the observed excess UFPN concentrations relative to other urban locations.

Correlations between short-term mobile monitoring and long-term passive sampler measurements of traffic-related air pollution.

Mobile monitoring has provided a means for broad spatial measurements of air pollutants that are otherwise impractical to measure with multiple fixed site sampling strategies. However, the larger the mobile monitoring route the less temporally dense measurements become, which may limit the usefulness of short-term mobile monitoring for applications that require long-term averages. To investigate the stationarity of short-term mobile monitoring measurements, we calculated long term medians derived from a mobile monitoring campaign that also employed 2-week integrated passive sampler detectors (PSD) for NOx, Ozone, and nine volatile organic compounds at 43 intersections distributed across the entire city of Baltimore, MD. This is one of the largest mobile monitoring campaigns in terms of spatial extent undertaken at this time. The mobile platform made repeat measurements every third day at each intersection for 6-10 minutes at a resolution of 10 s. In two-week periods in both summer and winter seasons, each site was visited 3-4 times, and a temporal adjustment was applied to each dataset. We present the correlations between eight species measured using mobile monitoring and the 2-week PSD data and observe correlations between mobile NOx measurements and PSD NOx measurements in both summer and winter (Pearson's r = 0.84 and 0.48, respectively). The summer season exhibited the strongest correlations between multiple pollutants, whereas the winter had comparatively few statistically significant correlations. In the summer CO was correlated with PSD pentanes (r = 0.81), and PSD NOx was correlated with mobile measurements of black carbon (r = 0.83), two ultrafine particle count measures (r =0.8), and intermodal (1-3 µm) particle counts (r = 0.73). Principal Component Analysis of the combined PSD and mobile monitoring data revealed multipollutant features consistent with light duty vehicle traffic, diesel exhaust and crankcase blow by. These features were more consistent with published source profiles traffic-related air pollutants than features based on the PSD data alone. Short-term mobile monitoring shows promise for capturing long-term spatial patterns of traffic-related air pollution, and is complementary to PSD sampling strategies.

Increased mortality associated with extreme-heat exposure in King County, Washington, 1980-2010.

Extreme heat has been associated with increased mortality, particularly in temperate climates. Few epidemiologic studies have considered the Pacific Northwest region in their analyses. This study quantified the historical (May to September, 1980-2010) heat-mortality relationship in the most populous Pacific Northwest County, King County, Washington. A relative risk (RR) analysis was used to explore the relationship between heat and all-cause mortality on 99th percentile heat days, while a time series analysis, using a piece-wise linear model fit, was used to estimate the effect of heat intensity on mortality, adjusted for temporal trends. For all ages, all causes, we found a 10% (1.10 (95% confidence interval (CI), 1.06, 1.14)) increase in the risk of death on a heat day versus non-heat day. When considering the intensity effect of heat on all-cause mortality, we found a 1.69% (95% CI, 0.69, 2.70) increase in the risk of death per unit of humidex above 36.0°C. Mortality stratified by cause and age produced statistically significant results using both types of analyses for: all-cause, non-traumatic, circulatory, cardiovascular, cerebrovascular, and diabetes causes of death. All-cause mortality was statistically significantly modified by the type of synoptic weather type. These results demonstrate that heat, expressed as humidex, is associated with increased mortality on heat days, and that risk increases with heat's intensity. While age was the only individual-level characteristic found to modify mortality risks, statistically significant increases in diabetes-related mortality for the 45-64 age group suggests that underlying health status may contribute to these risks.

Shift work and breast cancer among women textile workers in Shanghai, China.

PURPOSE: Although night-shift work has been associated with elevated risk of breast cancer in numerous epidemiologic studies, evidence is not consistent. We conducted a nested case-cohort study to investigate a possible association between shift work including a night shift and risk of breast cancer within a large cohort of women textile workers in Shanghai, China. METHODS: The study included 1,709 incident breast cancer cases and 4,780 non-cases. Data on historical shift work schedules were collected by categorized jobs from the factories, where the study subjects had worked, and then were linked to the complete work histories of each subject. No jobs in the factories involved exclusively night-shift work. Therefore, night shift was evaluated as part of a rotating shift work pattern. Hazard ratios and 95 % confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design for years of night-shift work and the total number of nights worked. Additionally, analyses were repeated with exposures lagged by 10 and 20 years. RESULTS: We observed no associations with either years of night-shift work or number of nights worked during the entire employment period, irrespective of lag intervals. Findings from the age-stratified analyses were very similar to those observed for the entire study population. CONCLUSIONS: The findings from this study provide no evidence to support the hypothesis that shift work increases breast cancer risk. The positive association between shift work and breast cancer observed in Western populations, but not observed in this and other studies of the Chinese population, suggests that the effect of shift work on breast cancer risk may be different in Asian and Caucasian women.

Ambient Ammonia Exposures in an Agricultural Community and Pediatric Asthma Morbidity.

BACKGROUND: Large-scale animal feeding operations compromise regional air quality in the rural US through emission of pollutants, such as ammonia gas. Exposure to airborne pollution from animal feeding operations may cause pediatric asthma exacerbations in surrounding communities. OBJECTIVES: To describe spatial and temporal patterns in ambient ammonia concentrations in an agricultural region, and to investigate associations between short-term fluctuations in ammonia and subsequent changes in respiratory health in children with asthma. METHODS: For 13 months in the Yakima Valley of Washington State, 14 monitors sampled ammonia in outdoor air for 24-hour periods every 6 days. School-age children with asthma (n = 51) were followed for two health outcomes: biweekly reports of asthma symptoms and quick relief medication usage, and daily measurements of forced expiratory volume in 1 second. We assessed associations between each outcome and ammonia using generalized estimating equations. RESULTS: Twenty-four-hour ammonia concentrations varied from 0.2 to 238.1 µg/m during the study period and displayed a strong correlation with proximity to animal feeding operations. The percentage of forced expiratory volume in 1 second was 3.8% lower (95% confidence interval = 0.2, 7.3) per interquartile increase in 1-day lagged ammonia concentration and 3.0% lower (95% confidence interval = 0.5, 5.8) for 2-day lagged concentration. We observed no associations between self-reported asthma symptoms or medication usage and estimated ammonia exposure. CONCLUSIONS: Ammonia concentrations were elevated in this community and strongly predicted by proximity to animal feeding operations. Ammonia's association with acute lung function decrements in children with asthma in the surrounding community may be causal or, alternatively, ammonia may be a marker for other pollutants from animal feeding operations associated with respiratory effects.

Regional PM2.5 and asthma morbidity in an agricultural community: a panel study.

BACKGROUND: Elevated pediatric asthma morbidity has been observed in rural US communities, but the role of the ambient environment in exacerbating rural asthma is poorly understood. OBJECTIVES: To investigate associations between particulate matter less than 2.5 µm in diameter (PM2.5) and pediatric asthma exacerbations in an agricultural community of Washington State. METHODS: School-aged children with asthma (n=58) were followed for up to 25 months with repeated measures of respiratory health. Asthma symptoms and quick-relief medication use were assessed biweekly through phone administered surveys (n=2023 interviews). In addition, subjects used home peak flow meters on a daily basis to measure forced expiratory volume in one second (FEV1) (n=7830 measurements). Regional PM2.5 was measured at a single air monitor located centrally in the study region. To assess relationships between PM2.5 and these outcomes we used linear regression with generalized estimating equations, adjusting for meteorological and temporal confounders. Effect modification by atopy was explored as well. RESULTS: An interquartile increase (IQR) in weekly PM2.5 of 6.7 µg/m(3) was associated with an increase in reported asthma symptoms Specific symptoms including wheezing, limitation of activities, and nighttime waking displayed the strongest associations. FEV1 as a percent of predicted decreased by 0.9% (95%CI: -1.8, 0.0) for an IQR increase in PM2.5 one day prior, and by 1.4% (95%CI: -2.7, -0.2) when restricted to children with atopic asthma. CONCLUSIONS: This study provides evidence that PM2.5 in an agricultural setting contributes to elevated asthma morbidity. Further work on identifying and mitigating sources of PM2.5 in the area is warranted.