NEAR-INSTANTANEOUS IMPACTS OF HIGH PM EPISODES ON CARDIOPULMONARY FUNCTION IN HEALTHY ADULTS PROJECT NUMBER: EH-05-02 HENK MEUZELAAR, NEIL ARNOLD, CRISTINA JARAMILLO AND KERRY KELLY, UNIVERSITY OF UTAH GERARDO MEJIA, JORGE GARCIA, JESUS SANTOS, MARCO MARTINEZ, MAXIMO SIERRA, AIDA ROJAS, ALEJANDRA ESTRADA AND NARDA RICHAUD, INSTITUTO TECNOLOGICO Y DE ESTUDIOS SUPERIORES DE MONTERREY WEN-WHAI LI, JESSICA JAMEZ, NANCY GARCIA AND DONALD BACA, UNIVERSITY OF TEXAS EL PASO INTRODUCTION Within the suburban and rural communities surrounding the sprawling Mexican border cities of Mexicali, Reynosa and Juarez, research teams supported by the Southwest Consortium for Environmental Research and Policy (SCERP) have repeatedly observed severe, transient evening PM episodes, with PM10 concentrations ranging from 250 to well over 1,000 µg/m3 for periods of up to four hours. Cumulative monitoring periods were analyzed totaling approximately eight days for designated areas in the direct vicinity of Mexicali (December 1993), Reynosa (December 1995), and Juarez (January 1999). Three such perimetropolitan particulate matter (“{PM}2”) episodes were reported, thereby indicating that high evening PM episodes are neither infrequent nor confined to a single border location (Mejia-Velazquez et al. 1997) Figure 1 shows seasonallyaveraged, hourly PM2.5 levels for the Sunmetro (a.k.a. CAMS40) site operated by the Texas Commission for Environmental Quality (TCEQ) near the border in El Paso. Evening PM episodes occur every two to four days, peaking around nineten pm at five to ten times higher concentration levels than average daytime levels, with average Fall/ Winter season evening peak levels exceeding Summer/Spring levels by about 20%. The majority of {PM}2 episodes recorded thus far reveal a common pattern of near-windless, nocturnal conditions with falling ambient temperatures and low-tozero mixing (inversion layer) heights. In late Spring and Summer the huge quantities of ambient PM produced by a bustling Mexican border metropolis during the evening traffic peak generally have a chance to disperse before pronounced atmospheric cooling and decreasing mixing layer heights produce stagnant conditions. However, during late Fall and Winter the combination of reduced solar heating and earlier sunsets starts producing stagnant conditions 1 before the evening traffic peak is completely over. This causes trapping of a thin, high density PM blanket close to the ground. In the course of the evening this dense, low laying PM cloud tends to slowly move down the Rio Grande river drainage as well as across adjacent suburban and rural areas driven by thermal drainage flows and related hydrodynamic forces, as explained by Fernando et al (2001), thereby apparently creating the observed {PM}2 events. Presumably, the {PM}2 episodes observed in suburban and rural areas represent only the tip of an iceberg as each of these events may be expected to correspond to a parent episode of at least equally high PM levels inside the metropolis. Additionally, there are likely to be episodes in which the PM cloud remains entirely stagnant, thus not leading to marked PM increases outside the perimeter. Because of a lack of time-resolved PM2.5 and PM10 monitoring data for Cd. Juarez and other Mexican border metropoli none of these assumptions can be readily verified. Due to their transient nature nocturnal {PM}2 events and their hypothetical urban parent episodes tend to remain hidden in standard 24-hr PM10 and PM2.5 measurement statistics. This prompts the question to what extent are short-lasting severe PM episodes likely to pose a substantial health threat, if any. As reviewed by Michaels and Kleinman (2000), observations on the physiological effects of PM on the human body, as well as on test animals, indicate that short term exposure to high PM levels can be associated with a host of physiological and pathological responses ranging from minor changes in cardiovascular or pulmonary performance to lifethreatening asthma attacks or allergic reactions and, therefore, should eventually lead to a new one hour PM exposure standard. A recent report by Peters et al. in the New England Journal of Medicine (2004) reveals a three times higher risk of heart attack in the first hour after being exposed to heavy traffic. Although there is as of yet insufficient data to affix the blame on urban PM exposure, the circumstantial evidence for such a link appears to be quite strong. Furthermore, in the Spring of 2002 the Principal Investigators carried out a SCERP-sponsored double-blind study of transient evening PM effects on cardiopulmonary function in five healthy young adults, as recorded at 30-minute intervals at the TCEQ Sodar site directly adjacent to the US/Mexican border. As detailed in a recent SCERP Monograph (Meuzelaar, et al), this study demonstrated the presence of strong associations between changes in PM 2.5 and, to a lesser extent, PM10 levels, as well as readily measurable changes in both Electrocardiography (ECG) patterns and spirometry profiles in subject A, a 25-year old male. Spirometry profile changes showed moderately decreased pulmonary performance whereas ECG pattern changes indicated reduced Heart Rate Variability. Of the remaining four subjects two appeared to show marginally detectable effects and the other two showed no measurable effects. However, only subject A and one of the marginal responders were monitored during a strong transient PM event. The other subjects happened to be monitored during relatively weak evening PM events. 2 RESEARCH OBJECTIVES To measure temporally-resolved (10-15 min interval) ambient PM2.5 and PM10 concentrations plus basic meteorology parameters for minimally four weeks at a central location in Cd. Juarez. This task will be carried out by Dr. Mejia’s team at the Instituto Tecnologica y de Estudios Superiores de Monterrey (ITESM), in collaboration with Dr. Li's University of Texas El Paso (UTEP) team. To measure sequential (30-min interval) ECG as well spirometry profiles of subjectively healthy volunteers at the same Cd. Juarez location during minimally one medium-to-high evening PM episode and one matched evening period with low-to-medium PM levels. Approximately 10 subjects will be monitored while exposed to ambient PM inside a fully screened, gazebo-style enclosure. This task will be carried out jointly by Dr. Santo (ITESM), Dr. Meuzelaar, University of Utah (UofU), and their co-workers. To correlate temporally-resolved PM2.5 and PM10 concentration data plus meteorological parameters with the corresponding cardiopulmonary timeseries data by means of advanced multivariate analysis techniques. RESEARCH METHODOLOGY/APPROACHES Current knowledge of the relationship between PM episodes and human health or fitness is primarily statistical in nature. There are disturbingly strong statistical correlations between episodes of high PM levels and high mortality levels in urban environments (Pope, et al 1992). Moreover, there are similar statistical correlations between high PM episodes and the number of patient visits to doctor’s offices and clinics (Vedal 1997). However, the precise mechanisms involved, as well as the possible relationships between particle composition and health effects, remain largely unknown. Until recently, the only emerging consensus was that individuals with already compromised cardiopulmonary systems were most readily affected. In 1998, however, Pope and co-workers (Pope, et al 1999) found measurable changes in HRV in elderly Utahns which correlated with ambient PM levels. This important observation, since then confirmed by several other research groups (A&WMA 2000), opened the area of statistically observable PM health effects up to systematic experimental verification. Compared to the above-referenced study by Pope et al (1999) in which correlations were observed between daily HRV measurements in six elderly people and regional ambient PM levels (as registered by outdoors monitoring stations), the research approach here makes use of the transient, high intensity character of the anticipated evening PM events. These are further analyzed by their presumptive parent episodes, to examine for near-instantaneous effects on 3 ECG and spirometry profiles, in up to 10 relatively healthy subjects while monitoring their personal ambient PM2.5 and PM10 exposure, as well as the chemical composition of the corresponding PM receptor samples. The limited scope of the proposed SCERP project permits a look at health effects among a small group of people in a highly specific environment and, therefore, should only be considered as a logical first step. Depending upon the outcome of the proposed project, future studies are likely to include elderly people and/or people with compromised cardio-pulmonary systems. A previous SCERP-sponsored study (Meuzelaar, et al) enabled the development of a battery of special preprocessing, exploratory analysis, data fusion and multivariate calibration techniques, which have already demonstrated the feasibility of the proposed approach by revealing a strong correlation between ECG plus spirometry time-series data and corresponding ambient PM data for one of five relatively healthy subject in their twenties. Based upon these findings at the TCEQ Sodar site in EL Paso, described in more detail in Chapter 7 of the most recent SCERP monograph (Meuzelaar, et al) a three-phase methodological approach is proposed: Phase 1 - During the late Fall/early Winter of 2005/2006, hourly PM10 and PM2.5 levels plus standard meteorological parameters (wind vectors, ambient temperature, atmospheric pressure, humidity and precipitation) will be measured by means of Dustrak and/or TEOM at the selected Cd. Juarez site for a minimum period of one month. As soon as the onset of a typical evening PM event is detected (defined by PM2.5 levels above 50 ug/m3 plus PM10/PM2.5 ratios of maximally 7.0 and wind speeds below 5 mph, in order to avoid windblown crustal PM events) a filter sampling system will collect PM samples for a maximum of two hours per filter or until a preset pressure differential is measured across the filter. Collected filter samples will be shipped to the ICES laboratory at the University of Utah for organic chemical characterization by thermal desorption (TD) GC/MS as well as inorganic characterization by means of X-Ray Fluorescence. Phase 2 - During a subsequent two to three week period the ITESM team will operate at the same site until several "genuine” evening PM events have been recorded. On low-wind afternoons around 1700 hrs, pre-selected and trained volunteer subjects will be asked to start recording ECG and spirometry profiles at 30-minute intervals while exposed to ambient PM levels inside a fully screened gazebo-style enclosure. In order to maintain double-blind test standards neither the subjects nor the local test operator or medical supervisor inside the enclosure will be given access to actual PM or meteorology data. Moreover, special lighting will prevent subjects and operator inside the enclosure from visually gauging ambient particulate matter levels. Meanwhile, the subjects will be encouraged to perform light physical tasks such as slow walking or bicycling using stationary exercise equipment. The goal is to obtain a minimum total of 12 measurement points per six hour long test period in order to obtain statistically 4 robust correlation coefficients between the various parameters. During subsequent days an attempt will be made to record a carefully matched nonevent control period with the same subjects. Only noninvasive, minimally intrusive, FDA-approved telemedical monitoring devices will be used under the supervision of a locally accredited physician or medical technician. Phase 3 - All cardiopulmonary response measurements, physicochemical PM characterization data and meteorological parameters will be integrated and correlated by the UofU team. This includes preparation of Fourier-transformed ECG traces and moment-transformed spirometer profiles, followed by Principal Component Analysis (PCA) based techniques such as orthogonal (e.g. Varimax and Discriminant) or oblique (e.g. Vardia) factor rotations, as well as multivariate calibration methods such as Principal Component Regression (PCR) and Canonical Correlation Analysis (CCA). As illustrated in SCERP Monograph #12 (Meuzelaar, et al) the specific sequences of multivariate data manipulations developed for the ECG, spirometry and PM concentration time-series, both alone and in various combinations, have proven to be effective tools for preprocessing, exploratory analysis, fusion and multivariate calibration of these particular sets of time-series data. For a more comprehensive explanation and overview of the various multivariate data analysis procedures used – which falls well outside the space limitations of the present report – the reader is again referred to Chapter 7 of SCERP monograph #12 (Meuzelaar, et al). PROBLEMS/ISSUES ENCOUNTERED The March 2006 monitoring period was exceptionally cold, windy and devoid of sizable PM evening peaks. The absence of detectable evening PM peaks prohibited the collection of meaningful ambient PM samples for organic and/or inorganic chemical speciation purposes. Moreover, due to the cold weather conditions, test subjects could not be exposed and monitored throughout the entire planned evening peak windows. Finally, some of the recorded data were lost due to a hard drive crash on one of the two laptops used (seemingly precipitated by the harsh ambient conditions). 5 RESEARCH FINDINGS While starting to set up for Phase 1 (PM monitoring) at the ITESM campus in Juarez during the second half of January 2006 it became clear that both Dr. Li’s (TEOM-type) PM2.5 and PM10 monitors would be needed on-site to distinguish between re-aerosolized PM peaks (caused by the frequent wind gusts) and typical evening PM peaks on the basis of differences in PM10/PM2.5 ratios. Although it would in principle have been possible to use Dr. Mejia’s five-channel Climet Optical Particle Counter (OPC) to calculate those ratios- after careful calibration against the TEOM monitors, the logistical problems of setting all three monitors up long enough in one and the same location (on either side of the border) in January proved insurmountable. Therefore, it was decided to use both TEOM monitors at the Juarez ITESM site during the Phase 2 PM exposure tests. These tests started on Feb 7 with the experimental set-up (see Figure 2) and the training/instruction of nearly a dozen volunteer tests subjects (ITESM students) by ITESM staff and students (see Figure 3), with on-site plus off-site assistance by UofU staff, whereas UTEP students installed the TEOM monitors. The first exposure tests were conducted on Feb 8 with four volunteer test subjects and were continued whenever weather conditions permitted. This produced additional measurements on Feb 9 (four test subjects), Feb 13 (four test subjects), Feb 20 (five test subjects), Feb 21 (three test subjects), and Feb 22 (five test subjects). Because of the exceptionally cold and windy weather, with temperatures repeatedly plunging into the low 40s (not counting wind chill factors) during the second half of the evening, the six-hour test window for obtaining half-hourly ECG and spirometry measurements had to be set between 1600 and 2200 hours rather than between 1700 and 2300 hrs, as originally planned. The PM data recorded during these test periods are shown in Figures 4-9. Between Feb 8 and 22, a total of 25 ECG (figure 10) and spirometer (Figure 11) time-series were recorded on 11 “healthy” subjects. The protracted windy conditions not only caused long test delays, e.g. between Feb 13 and Feb 20, but effectively prevented the evolution of marked evening PM events. A serious additional problem was encountered when one of the two laptop computers used in the field experiment suffered a disk crash. Although all test data had been backed up on a regular basis, it later turned out that the ECG monitor software saves some key file directory information in a different location and that without this information it is impossible to use the recorded ECG data. All in all, about 30 % of the recorded ECG profiles were affected. Nearly three weeks after the various teams had started, the field experiments had to be concluded because of budgetary restrictions and continued poor, or at 6 best marginal, weather forecasts. The subsequent Phase 3 data integration and analysis work by the UofU team (assisted by two ITESM team members who visited for two weeks to help put the finishing touches on this phase of the work) confirmed that the ECG and spirometry data obtained during this entire test period were indeed inconclusive, with none of the participants showing statistically significant correlations between ECG profiles and measured PM levels. Since none of the evenings saw PM2.5 levels above 30 µg/m3 Meanwhile however, marked progress had been achieved with the continued development and testing of advanced ECG monitoring and FFT signal conversion techniques. The new method, called “ECGIII” and developed by Neil Arnold (UofU) can be applied to the old (King of Hearts) ECG monitors used in 2002, as well as the new ECG@home devices (Figure 10) used in the current set of experiments. It automatically detects and selects “n” cardiac cycles to eliminate the potential bias introduced by the slightly subjective and much more laborious manual selection method. When used with the 2002 data set the observed correlations are stronger. Moreover, application of the relatively new Positive Matrix Factorization (PMF) method, developed by Hopke and associates (2000) to the FFT-data from 2002 test subject A was shown to provide a clearer view of the possible physical mechanisms underlying the observed strong covariance between ECG, spirometry and PM changes in the data than produced thus far by the PCA and PCR-based approaches reported in SCERP monograph #12 (Meuzelaar, et al). Figure 12 shows the important contribution of low-frequency FFT components during high PM episodes, confirming the findings of HRV studies using simple heart rate monitors (Vedal 1997, Pope 1999, Holquin, et al 2003), while also revealing that at least two different PMF factors show strong higher frequency effects that necessarily remain hidden in low bandwidth heart rate monitor experiments but appear to be brought out by the much higher bandwidths of ECG time-series data. Last but not least, the feasibility of low-budget, collaborative, capacity-building experiments involving students, staff and faculty from three different SCERP partner institutions was successfully demonstrated under very trying environmental conditions. CONCLUSIONS Due to a lack of marked PM events throughout the Feb ‘06 monitoring period the new data are inconclusive regarding the presence of cardiopulmonary responses in other young adults. Meta-analysis of the 2002 data confirms the statistical and mechanistic significance of the fast, reversible PM response in our ECG and spirometry profiles of a 25-yr old test subject. 7 Low-cost, home-ECG monitors can be modified for time-series ambient monitoring, thus providing wide-band, multi-parameter data at the cost of a simple heart-rate monitor. Positive Matrix Factorization (PMF) of FFT-coverted ECG time-series is shown to be a promising tool for exploring underlying components, trends and potential mechanisms. RECOMMENDATIONS FOR FURTHER RESEARCH It is recommended that future PM exposure studies along the US-Mexico border are conducted, but that they involve more highly vulnerable test subjects. Researchers and analysts will need to keep in mind that strong cardiopulmonary responses might be observed. In order to accelerate the understanding of PMrelated cardiopulmonary mortality and morbidity, the use of MDA-enhanced ECG & spirometry is recommended over heart rate monitoring alone. RESEARCH BENEFITS The reported exceptional weather conditions during the field test period have prevented the occurrence of strong enough evening PM events to enable effective testing of possible heart (ECG) and lung (spirometry) responses among the eleven “subjectively healthy” test subjects. Consequently, this study has been unable to confirm the earlier finding of near-instantaneous ECG and spirometry responses among one of five test subjects exposed to a characteristically high evening PM event in the PdN airshed during a similar SCERP-funded study carried out in 2002. In spite of the inconclusive field test results, the present study has produced important benefits for regional, transboundary or international research into the health effects of ambient PM levels, namely development and application of: highly informative field-test procedures for potential heart (ECG) and lung (spirometry) responses using affordable home-medical monitoring devices; efficient signal conditioning plus Fourier-transform-based pre-processing techniques for ECG and spirometry data; and advanced multivariate analysis methods such as Positive Matrix Factorization (PMF). Availability of these improved research techniques will enable SCERP and non-SCERP researchers alike to study near-instantaneous as well as long-term health effects of ambient PM hereto inaccessible to systematic investigation. 8 Perhaps most importantly, the work reported here has demonstrated the feasibility of designing and carrying out complex, collaborative field projects in which research teams from several university campuses on both sides of the border completed their assigned measurement tasks, notwithstanding the extremely challenging weather conditions. This has resulted in significant capacity building for the participating, SCERP-sponsored US-Mexican border institutions. The results of this research project have been presented in the form of a talk and a poster (Figure 12) at the December 12-13, 2006 SCERP Technical Meeting in Tucson, Arizona. ACKNOWLEDGMENTS The expert advice of Joanne Lighty and Adel Sarofim, as well as the technical support of Dana Overacker are gratefully acknowledged This work was sponsored by the Southwest Consortium for Environmental Research and Policy (SCERP) through a cooperative agreement with the U.S. Environmental Protection Agency. SCERP can be contacted for further information through www.scerp.org and scerp@mail.sdsu.edu. 9 REFERENCES A&WMA Conference on “PM2000: Particulate Matter and Health”, January 2000, Charleston (SC), USA (multiple platform and poster presentations). Chueinta, W., Hopke, P.K., Paatero, P.; “Investigation of Sources of Atmospheric Aerosol Urban and Suburban Residential Areas in Thailand by Positive Matrix Factorization”, Atmospheric Environ., 34, 3319 (2000). Fernando, H.J.S., S.M. Lee, J. Anderson, M. Princevac, E. Pardyjak, and S. 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