2015 Progress Report: Vascular Response to Traffic-Derived Inhalation in Humans

EPA Grant Number: R834796C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R834796
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: University of Washington Center for Clean Air Research
Center Director: Vedal, Sverre
Title: Vascular Response to Traffic-Derived Inhalation in Humans
Investigators: Kaufman, Joel D. , Larson, Timothy V.
Institution: University of Washington , Lovelace Respiratory Research Institute
EPA Project Officer: Callan, Richard
Project Period: December 1, 2010 through November 30, 2015 (Extended to November 30, 2017)
Project Period Covered by this Report: August 1, 2014 through July 31,2015
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

Project 4 examines the acute vascular effects of commute traffic exhaust exposures in human subjects in a multipollutant context. This double-blind, randomized controlled crossover trial will test whether traffic-derived mixed pollution atmospheres of diesel exhaust and gasoline engine exhaust, experienced through travel on roadways in a passenger car, causes an increased vascular response (brachial artery vasoconstriction, increased blood pressure, reduced retinal arteriolar diameter) compared with filtered air (FA) in healthy subjects. Nested aims include whether specific exhaust-related monocytic gene expression effects are mediated by lipid peroxidation; whether traffic-related pollutants’ vasoconstrictive effects are increased in subjects with a common SNP variant in the gene coding for TRPV1; and whether monocyte DNA methylation in specific genes is modified with exposure to typical, roadway-derived exposures.

Progress Summary:

Project 4 was launched in Year 4 of the Center. In this project, we use a "“typical commute”" study design and pertinent experience in human exposure studies to advance the Center’'s research agenda with a double-blind controlled exposure crossover clinical trial in 16 subjects, randomized to order. Using an innovative approach in which contrasts of in-vehicle exposure and potential participant susceptibility by genotype are nested in the experiment, we can address several hypotheses in this study. Building on our prior work, we will use a typical commute model to confirm or determine whether traffic-derived aerosols (e.g., mixed on-road environment with diesel and gasoline engine exhaust components) (1) exert demonstrable and important acute vascular effects in human subjects, (2) acutely induce increased lipid peroxidation and response to oxidized phospholipids, and (3) result in measurable impacts on gene expression and DNA methylation in pathways that are related not only to the triggering of acute cardiovascular events but also to the development and progression of atherosclerosis. All of the outcomes we measure are completely transient and reversible, and exposures are designed to be those of a typical urban commute path.

Screening

Subjects are screened to determine eligibility. At screening, subjects are required to be in the normal range for BMI, blood sugar, cholesterol and triglyceride levels, lung function, blood pressure, and ECG. Subjects also fill out questionnaires describing past illness, health history, traffic and chemical exposure, smoking history, and occupation. Buccal swab samples are collected in order to achieve a balance of the TRPV1 (SNP I-585V) gene, which is related to responsiveness to traffic-related air pollution.

Eligible subjects are randomized to three 2-hour commutes that travel I-5, extending from North Seattle to roadways in South Seattle (e.g., Duwamish Valley). During each drive, subjects are accompanied by research staff responsible for collecting subject health measurements and monitoring conditions of the drive. Each drive is separated by at least 3 weeks. During drives, the cabin air and HEPA filters are configured to reflect the randomized exposure conditions (i.e., on-road ambient or filtered air exposure). The cabin ventilation controls are adjusted such that air is entrained and directed to the floor vents, and the temperature inside the vehicle is comfortable for the occupants. Van windows remain closed during the drive and subjects wear N95 masks while transitioning from the lab to the University of Washington (UW) van regardless of drive condition.

Enrollment

To date, three subjects have completed all three drives, and one subject has dropped out. Nineteen subjects have been screened and 15 are waitlisted to begin.

Health Measurements

Subjects complete health measurements at baseline, during the drive, immediately after the drive, 3 hours later, 5 hours later and 24 hours later. These health measurements include questionnaires, blood markers, Holter ECG, ambulatory blood pressure, 24-hour urine, brachial artery reactivity, retinal photography and Finometer measurements. The frequency of health measurements are shown in Table 1. All subjects provide a urine sample for a cotinine test and, if female, a pregnancy test.

Table 1. Experimental Session Timeline for the Center for Clean Air Research (CCAR), Project Four
AM/PM AM PM
Time (hour) 10:00pm-7:00 am 7:00 8:00 9:00 10:00 11:00 12:00 1:00 2:00 3:00 4:00   9:00 am
(24hr)
Overnight fast X                       X
Urine collection   X X X X X X X X X X X X
Vitals BP, PR, RR   X   XX XXX   X   X   X   X
ABP             X X X X X X X
Holter Monitor 11 min record   XX X X XX X XX X X X XX X XX
Blood Draw     X               X   X
BAR Roosevelt     X     X              
Symptom Questions     X   X   X   X   X   X
Commute Drive                          
Finometer     X X X X X   X   X   X
Retinal Photography     X     X              
Lunch             X            

Air Monitoring

This study involves in-vehicle monitoring for 48 drives involving 16 participants in Seattle. Each day of monitoring will include the following suite of monitors in order to collect real-time measurements of the pollutants: PM2.5 (Nephelometer, Radiance Research), black carbon (microAethelometer, Aeth Labs), particle count (P-Trak, TSI Inc.), PAHs (PAS 2000CE, EcoChem), NO2 (CAPS, Aerodyne Research Inc.), NOx (UV absorbance Model 410, 2B Technologies), ozone (chemiluminescence 3.02P, Optec), CO (CO T15n, Langan), CO2 (CO2 K-30-FS Sensor, CO2Meter.com), temp/RH (Precon HS-2000, Kele Precision Manufacturing), location (GPS BU-353, USGlobalSat). Filters and air monitors inside the car are powered by gel cell batteries connected to power inverters.

Pilot Testing

During the last year, the Center for Clean Air Research (CCAR) Project 4 prepared and extensively pilot tested the UW vehicle in order to provide reduced particle counts and black carbon concentrations to participants. The pilot data from these drives is summarized below.

The on-road concentrations of some air pollutants can be dramatically higher than concentrations of the same pollutants even a short distance from a major roadway. These pollutant gradients are one of the rationales for conducting on-road measurements inside a vehicle where the study subject can have both physiological responses and air pollutant exposures characterized. Important operational concerns include the ability to create a different “:control"” no- or minimal-exposure case for baseline comparison with the pollutant exposure situation. The areas with high traffic-related pollutants need to be identified so a route can be formulated that will take the subject through areas where the on-road concentrations of pollutants are significant.

Toward these ends, we conducted pilot studies that began with an assessment of pollutant exposures along major highways in the Seattle area and then continued with an investigation of methods for distinguishing the clean, filtered-air control case from the exposure condition inside the vehicle. Multiple test drives were conducted to refine the route with exposure to higher concentrations, and to diesel exhaust from heavy truck traffic specifically.

Drive Route Location

The air monitoring system inside the vehicle is adapted from a mobile monitoring study conducted in CCAR Project 1 in five cities throughout the nation from 2011 to 2013. The initial route characterization pilot study for Project 4 was conducted in December 2012. Pollutants were measured outside the vehicle as it was driven on major limited-access highways. Geographic plots coded by quintile of the particle count larger than 50 nm and the fine PM relative concentration by light scattering are shown in Figures 1 and 2, respectively.

The initial 3 days of drives in 2012 confirmed that I-5 through downtown Seattle experiences high levels of particulate matter concentration and particle counts. This information, coupled with logistical concerns about maintaining a consistent 2-hour exposure time for the subject in the vehicle, led us to focus on the I-5 corridor past downtown Seattle as a principal part of the commute exposure drive route. The route also goes past the Washington Department of Ecology’'s recently deployed near-road air monitoring station at 10th Avenue South and South Weller Street on the east side of I-5.

We used results from mobile monitoring conducted for the Diesel Exhaust Exposure in the Duwamish Study (DEEDS) to identify the Port of Seattle freight truck terminal access routes as an area of interest with higher than normal levels of diesel engine exhaust. A segment of the drive route was added that loops past the truck terminal entrances at the south end of Harbor Island and underneath the West Seattle Bridge. The route shown in Figure 3, which displays particle count by quintile measured inside the vehicle without filtration in place, was selected for its highway pollutant levels along I-5, the higher incidence of diesel engine exhaust by Harbor Island, and ease of access to and from the University of Washington clinic to enable consistent duration exposure sessions among subjects regardless of traffic conditions on a given exposure day.


Figure 1. Particle count quintiles during December 2012 mobile monitoring drive in Seattle area. Routes traveled included I-5 past downtown Seattle as far south as Southcenter, I-405 between Southcenter and the northern edge of downtown Bellevue, and both I-90 and SR 520 across Lake Washington between the two north-south routes.


Figure 2. PM2.5 proxy measurements by light scattering nephelometer presented in quintiles during December 2012 mobile monitoring drive in Seattle area.
Routes traveled included I-5 past downtown Seattle as far south as Southcenter, I-405 between Southcenter and the northern edge of downtown Bellevue, and both I-90 and SR 520 across Lake Washington between the two north-south routes.


Figure 3. Particle count quintiles during October 2014 in-vehicle monitoring drive along the consolidated Seattle route selected for the subject commute exposure study on-road sessions.

Filtration to Ensure Control Case

With the study designed to compare the physiological effects from exposure and filtered air scenarios, a reliable and consistent way of ensuring a large difference in exposure levels is needed to distinguish the resultant effects. For the filtered air case, we chose to use supplemental filtration in addition to the vehicle'’s own ventilation system filter. The pilot study first evaluated an existing HEPA filtration unit that had been used for filtering particulate matter in previous exposure and control studies. The Honeywell Envircaire, model 11520 unit, is configured to discharge filtered air in a circular pattern radiating away from its round housing. This presented challenges for use in the cabin of the Caravan to direct as much of the filtered air as possible toward the subject in the left-side middle row passenger seat. Baffles were used to narrow the discharge to a smaller cross-sectional area where instruments were positioned to evaluate the Envircaire unit performance in reducing particle loadings. A comparison of averaged PM measurements both with and without the filtration media inside the device found the following reductions of particulate matter in the filtered air scenario relative to the no-filtration configuration:

 

  Particle Count, by P-Trak

33.6%

  Black Carbon Conc., by microAeth

66.2%

Improved particulate matter reduction was sought by using another HEPA filter unit designed to discharge its filtered air stream in one direction at the top of the rectangular cross-section device. This Whirlpool Whispure model AP51030K proved to be more effective at reducing particle loadings at higher fan speeds than the Enviracaire unit, as indicated by these particle count reductions measured by a P-Trak and black carbon concentration differences by microAeth at four different HEPA unit fan speeds:

  HEPA Fan speed:

Low

Medium

High

Turbo

  Particle Count Reduction

46.1%

51.1%

55.5%

60.4%

  Black Carbon Reduction

47.8%

60.6%

68.5%

74.9%

The Whispure performance for light-scattering–-based fine PM was only 29 percent to 43 percent reduction in scattering coefficient (by nephelometer) as the fan speed varied from low to turbo setting. Entrainment of nonfiltered air into the discharged stream of filtered air was a significant cause of lowering the particle removal efficiency based on varying the inlet location of the particle instruments in real time. The effect of entrained air mixing with the HEPA unit discharge stream was evident for measurements only 6 inches from the Whispure outlet air discharge, as shown in Figure 4. By comparison, the particle removal efficiency was much better when the measurements were made in the directed air stream exiting the HEPA discharge vent by using a baffle or straight stream line diffuser, as illustrated in Figure 5.


Figure 4. Comparison of nonfilter and filter conditions in discharge from Whispure HEPA unit for configuration where entrainment of nonfiltered air affects the particulate removal efficiency.


Figure 5. Comparison of nonfilter and filter conditions in discharge from Whispure HEPA unit with streamlines maintained to minimize the influence of nonfiltered air entrainment.

To ensure the filtered air at the subject’s breathing zone is characterized by high particle-removal efficiency compared with the exposure scenario, the streamlines of the air exiting the HEPA filter need to be maintained in a laminar, straight-line condition to prevent entrainment of surrounding air that is not HEPA filtered. By measuring the particulate levels in the discharge air stream with and without the filtration elements in the HEPA unit, we found the Whispure could achieve high levels of particulate matter removal. At medium fan speed, we found these reductions to be

  Particle Count, by P-Trak

96%

  PM Light Scattering, by Nephelometer

73%

  Black Carbon Conc., by microAeth

71%

The Whispure HEPA filter was therefore used to provide the particulate matter removal inside the study vehicle for creating the “filtered air” scenario that serves as the control case against which the exposure conditions can be compared. It is subsequently equipped with a manifold to gather the discharge flow, which then is conveyed via a flex duct to a straight streamline diffuser, which is directed toward the subject'’s breathing zone and the instrument inlets next to the subject’'s shoulder.


Figure 6. Sequential comparison of particulate matter levels inside study Caravan during on-highway drive.

Reduction of gaseous pollutants is not nearly as effective as particulate matter. Sorption of vapors by use of a specialized baking soda and activated charcoal filter in place of the standard vehicle ventilation system filters is the means of gas reduction for the control filtered air scenario. The contact time is short for the air flow passing through this filter, so the reduction efficiencies observed for the particles cannot be realized for gaseous pollutants. Still, we have been able to show a 24 percent reduction in NO2 as measured inside the vehicle by the Aerodyne CAPS analyzer relative to the full exposure configuration, in which both the vehicle ventilation filter and HEPA unit filter element are removed.

Future Activities:

We plan to continue the commute exposure study in Year 5 and complete it during the no-cost extension year, and we will conduct all health analyses in the no-cost extension year.


Journal Articles on this Report : 1 Displayed | Download in RIS Format

Other subproject views: All 1 publications 1 publications in selected types All 1 journal articles
Other center views: All 166 publications 74 publications in selected types All 73 journal articles
Type Citation Sub Project Document Sources
Journal Article Cosselman KE, Navas-Acien A, Kaufman JD. Environmental factors in cardiovascular disease. Nature Reviews Cardiology 2015;12(11):627-642. R834796 (2015)
R834796C004 (2015)
  • Abstract from PubMed
  • Abstract: Nature Reviews Cardiology-Abstract
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  • Supplemental Keywords:

    Health, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, Air Quality, air toxics, Health Risk Assessment, Risk Assessments, mobile sources, Biochemistry, Risk Assessment, ambient air quality, atmospheric particulate matter, particulate matter, aerosol particles, air pollutants, motor vehicle emissions, vehicle emissions, air quality models, motor vehicle exhaust, airway disease, bioavailability, air pollution, particle exposure, atmospheric aerosols, ambient particle health effects, vascular dysfunction, cardiotoxicity, atmospheric chemistry, exposure assessment

    Relevant Websites:

    Center for Clean Air Research Exit

    Progress and Final Reports:

    Original Abstract
    2011 Progress Report
    2012 Progress Report
    2013 Progress Report


    Main Center Abstract and Reports:

    R834796    University of Washington Center for Clean Air Research

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834796C001 Exposure Mapping – Characterization of Gases and Particles for ExposureAssessment in Health Effects and Laboratory Studies
    R834796C002 Simulated Roadway Exposure Atmospheres for Laboratory Animal and Human Studies
    R834796C003 Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions
    R834796C004 Vascular Response to Traffic-Derived Inhalation in Humans
    R834796C005 Effects of Long-Term Exposure to Traffic-Derived Particles and Gases on Subclinical Measures of Cardiovascular Disease in a Multi-Ethnic Cohort