Air pollution, physical activity, and markers of acute airway oxidative stress and inflammation in adolescents

Background: The airway inflammatory response is likely the mechanism for adverse health effects related to exposure to air pollution. Increased ventilation rates during physical activity in the presence of air pollution increases the inhaled dose of pollutants. However, physical activity may moderate the relationship between air pollution and the inflammatory response. The present study aimed to characterize, among healthy adolescents, the relationship between dose of inhaled air pollution, physical activity, and markers of lung function, oxidative stress, and airway inflammation. Methods: With a non-probability sample of adolescents, this observational study estimated the association between air pollution dose and outcome measures by use of general linear mixed models with an unstructured covariance structure and a random intercept for subjects to account for repeated measures within subjects. Results: A one interquartile range (IQR) (i.e., 345.64 µg) increase in ozone (O3) inhaled dose was associated with a 29.16% average decrease in the percentage of total oxidized compounds (%Oxidized). A one IQR (i.e., 2.368E+10 particle) increase in total particle number count in the inhaled dose (PNT) was associated with an average decrease in forced expiratory flow (FEF25-75) of 0.168 L/second. Increasing activity levels attenuated the relationship between PNT inhaled dose and exhaled nitric oxide (eNO). The relationship between O3 inhaled dose and percent oxidized exhaled breath condensate cystine (%CYSS) was attenuated by activity level, with increasing activity levels corresponding to smaller changes from baseline for a constant O3 inhaled dose. Conclusions: The moderating effects of activity level suggest that peaks of high concentration doses of air pollution may overwhelm the endogenous redox balance of cells, resulting in increased airway inflammation. Further research that examines the relationships between dose peaks over time and inflammation could help to determine whether a high concentration dose over a short period of time has a different effect than a lower concentration dose over a longer period of time

A Novel Method for Quantifying the Inhaled Dose of Air Pollutants Based on Heart Rate, Breathing Rate and Forced Vital Capacity

To better understand the interaction of physical activity and air pollution exposure, it is important to quantify the change in ventilation rate incurred by activity. In this paper, we describe a method for estimating ventilation using easily-measured variables such as heart rate (HR), breathing rate (fB), and forced vital capacity (FVC). We recruited healthy adolescents to use a treadmill while we continuously measured HR, fB, and the tidal volume (VT) of each breath. Participants began at rest then walked and ran at increasing speed until HR was 160–180 beats per minute followed by a cool down period. The novel feature of this method is that minute ventilation (V_ E) was normalized by FVC. We used general linear mixed models with a random effect for subject and identified nine potential predictor variables that influence either V_ E or FVC. We assessed predictive performance with a five-fold cross-validation procedure. We used a brute force selection process to identify the best performing models based on cross-validation percent error, the Akaike Information Criterion and the p-value of parameter estimates. We found a two-predictor model including HR and fB to have the best predictive performance (V_ E/FVC = -4.247+0.0595HR+0.226fB, mean percent error = 8.1±29%); however, given the ubiquity of HR measurements, a one-predictor model including HR may also be useful (V_ E/FVC = -3.859+0.101HR, mean percent error = 11.3±36%)

Modification of Traffic-related Respiratory Response by Asthma Control in a Population of Car Commuters

Background: Effects of traffic-related exposures on respiratory health are well documented, but little information is available about whether asthma control influences individual susceptibility. We analyzed data from the Atlanta Commuter Exposure study to evaluate modification of associations between rush-hour commuting, in- vehicle air pollution, and selected respiratory health outcomes by asthma control status. Methods: Between 2009 and 2011, 39 adults participated in Atlanta Commuter Exposure, and each conducted two scripted rush-hour highway commutes. In-vehicle particulate components were measured during all commutes. Among adults with asthma, we evaluated asthma control by questionnaire and spirometry. Exhaled nitric oxide, forced expiratory volume in 1 second (FEV1), and other metrics of respiratory health were measured precommute and 0, 1, 2, and 3 hours postcommute. We used mixed effects linear regression to evaluate associations between commute-related exposures and postcommute changes in metrics of respiratory health by level of asthma control. Results: We observed increased exhaled nitric oxide across all levels of asthma control compared with precommute measurements, with largest postcommute increases observed among participants with below-median asthma control (2 hours postcommute: 14.6% [95% confidence interval {CI} = 5.7, 24.2]; 3 hours postcommute: 19.5% [95% CI = 7.8, 32.5]). No associations between in-vehicle pollutants and percent of predicted FEV1 were observed, although higher PM2.5 was associated with lower FEV1 % predicted among participants with below-median asthma control (3 hours postcommute: -7.2 [95% CI = -11.8, -2.7]). Conclusions: Level of asthma control may influence respiratory response to in-vehicle exposures experienced during rush-hour commuting

Particulate metal exposures induce plasma metabolome changes in a commuter panel study

Introduction Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. Methods A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. Results HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. Conclusions Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation

Source-specific pollution exposure and associations with pulmonary response in the Atlanta Commuters Exposure Studies

Concentrations of traffic-related air pollutants are frequently higher within commuting vehicles than in ambient air. Pollutants found within vehicles may include those generated by tailpipe exhaust, brake wear, and road dust sources, as well as pollutants from in-cabin sources. Sourcespecific pollution, compared to total pollution, may represent regulation targets that can better protect human health. We estimated source-specific pollution exposures and corresponding pulmonary response in a panel study of commuters. We used constrained positive matrix factorization to estimate source-specific pollution factors and, subsequently, mixed effects models to estimate associations between source-specific pollution and pulmonary response. We identified four pollution factors that we named: crustal, primary tailpipe traffic, non-tailpipe traffic, and secondary. Among asthmatic subjects (N=48), interquartile range increases in crustal and secondary pollution were associated with changes in lung function of −1.33% (95% confidence interval (CI): −2.45, −0.22) and −2.19% (95% CI: −3.46, −0.92) relative to baseline, respectively. Among non-asthmatic subjects (N=51), non-tailpipe pollution was associated with pulmonary response only at 2.5 hours post-commute. We found no significant associations between pulmonary response and primary tailpipe pollution. Health effects associated with traffic-related pollution may vary by source, and therefore some traffic pollution sources may require targeted interventions to protect healt

Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters

Background Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. Objectives: We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. Methods We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects’ private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. Results At measurement time points within 3 h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p \u3c 0.0001). Conclusions Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute

Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma

-nitrosothiols (SNOs), a class of endogenous airway smooth muscle relaxants. This deficiency results from increased activity of an enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway SNOs is related to asthma pathology, and breath formate concentration may be a proxy measure of SNO catabolism. (r = −0.39, p = 0.002, asthmatics only), and positively correlated with the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not significantly correlated with other volatile organic acids nor with inhaled corticosteroid dose.-nitrosothiols

Real-time measurement of the water-insoluble aerosol size distribution: instrument development and implementation

This thesis concerns various aspects of the influence of atmospheric particulate matter on the terrestrial system. In Part I, the radiative influence of particulate matter on the production of crops is explored using the CERES crop model. It is known that the presence of aerosols in the atmosphere simultaneously reduces the amount of sunlight reaching the surface and increases the fraction of that light which is diffuse. Reduction of the total amount of sunlight tends to slow the rate of photosynthesis occurring in plants while increasing the fraction which is diffuse tends to increase the net rate of photosynthesis by more evenly distributing sunlight throughout all layers of a plant canopy. The CERES crop model was modified to estimate the influence of both a reduction in total sunlight and an increase in the diffuse fraction. Model simulations were performed for rice, maize and wheat at a variety of locations and found the likely influence of aerosols on crop production to be a 0-10% reduction in yield compared to the base case. In Part II, the concentration and size distribution of water-insoluble aerosols (WIA) is explored. It has been well-established that atmospheric particulate matter influences the planetary radiation budget both directly and indirectly. The magnitude of these influences is related to particle solubility. A new technique was developed to provide these measurements in real-time. This instrumentation was evaluated in a laboratory setting and implemented into several field studies. Results from these sampling campaigns indicate that in areas heavily influenced by motor vehicle traffic, the WIA concentration is dominated by particulate soot. Many episodes of high levels of crustal dust were also observed. At these times, the WIA size distribution shifted toward larger sizes in a characteristic manner. This suggests that this method is useful for detecting insoluble mineral aerosols as well as particulate soot and that examination of the WIA size-distribution may provide a basis to distinguish between the two.Ph.D.Committee Chair: Michael H. Bergin; Committee Member: Armistead Russell; Committee Member: James Mulholland; Committee Member: Jean-Luc Jaffrezo; Committee Member: Rodney Webe

The impact of vegetative and solid roadway barriers on particulate matter concentration in urban settings.

A potentially important approach for reducing exposure to traffic-related air pollution (TRAP) is the use of roadside barriers to reduce dispersion from highway sources to adjacent populated areas. The Trees Reducing Environmental Exposures (TREE) study investigated the effect of vegetative and solid barriers along major controlled-access highways in Atlanta, Georgia, USA by simultaneously sampling TRAP concentration at roadside locations in front of barriers and at comparison locations down-range. We measured black carbon (BC) mass concentration, particle number concentration (PNC), and the size distribution of ultrafine aerosols. Our sample sites encompassed the range of roadway barrier options in the Atlanta area: simple chain-link fences, solid barriers, and vegetative barriers. We used Generalized Linear Mixed Models (GLMMs) to estimate the effect of barrier type on the ratio of particle concentrations at the comparison site relative to the roadside site while controlling for covariates including wind direction, temperature, relative humidity, traffic volume, and distance to the roadway. Vegetative barriers exhibited the greatest TRAP reduction in terms of BC mass concentration (37% lower behind a vegetative barrier) as well as PNC (6.7% lower), and sensitivity analysis was consistent with this effect being more pronounced when the barrier was downwind of the highway. The ultrafine size distribution was comprised of modestly smaller particles on the highway side of the barrier. Non-highway particle sources were present at all sample sites, most commonly motor vehicle emissions from nearby arterials or secondary streets, which may have obscured the effect of roadside barriers