Final Report: Acute Cardiopulmonary Responses to Fine Particulate Pollution and Copollutant Oxidant Gases in Los AngelesEPA Grant Number: R827999
Title: Acute Cardiopulmonary Responses to Fine Particulate Pollution and Copollutant Oxidant Gases in Los Angeles
Investigators: Gong, Henry , Sioutas, Constantinos
Institution: University of Southern California , Rancho Los Amigos Medical Center
EPA Project Officer: Chung, Serena
Project Period: March 15, 2000 through March 14, 2003 (Extended to January 14, 2004)
Project Amount: $613,894
RFA: Airborne Particulate Matter Health Effects (1999) RFA Text | Recipients Lists
Research Category: Air , Health Effects , Particulate Matter
The objectives of this research project were to:
- Perform controlled exposures of human volunteers to urban ambient particulate matter (PM) in combination with a common oxidant pollutant gas—nitrogen dioxide (NO2)— representing an extreme but still realistic combination of exposure conditions and vulnerable people. The experimental atmospheres were: (1) filtered air (FA) (control condition); (2) 400 ppb NO2; (3) approximately 200 μg/m3 concentrated ambient fine PM; and (4) NO2 in combination with concentrated PM at the concentration mentioned. The volunteer subjects were healthy elderly adults and elderly adults with chronic obstructive pulmonary disease (COPD).
- Document short-term effects of the above exposures on measures of cardiopulmonary health and systemic inflammation. The endpoints include symptom inventories, clinical respiratory function (e.g., forced expiratory spirometry, pulse oximetry), airway inflammation in samples of induced sputum, systemic inflammation and hemostasis in samples of peripheral blood, and cardiac rhythm alterations from continuous ambulatory electrocardiograms.
The investigation was conducted in a Los Angeles suburb with generally high levels of primary particulate pollution, predominantly from gasoline- and diesel-powered motor vehicles, and with relatively low levels of secondary photochemical aerosol. Of six healthy elderly volunteers, all completed the entire protocol of four exposure studies. Of 22 initial volunteers with COPD, 4 withdrew before providing usable data, 16 completed all exposures, 1 completed three, and 1 completed two. These two incomplete subjects were retained in data analyses, which employed maximum-likelihood estimations of missing data. Withdrawals were not related to effects of exposure, as far as could be determined from exit interviews.
A two-stage Harvard particle concentrator was used to enrich fine ambient particles (0.1-2.5 µm aerodynamic diameter) to as much as eight times the prevailing ambient level. In general, the concentrator system achieved consistent concentrations near the target of 200 µg/m3 (averaged over 2-hour exposure periods) in the single-person exposure chamber. Occasionally, an exposure to concentrated ambient particles (CAPs) was rescheduled because unusually low ambient PM pollution made it impossible to reach the target exposure concentration. As a result, there was a significant difference in prior ambient PM exposure concentrations between exposures with CAPs (i.e., exposures to CAPs alone or to CAPs + NO2) and those without CAPs (i.e., exposures to FA alone or NO2 alone). The only other relevant issue encountered occasionally with the particle concentrator was a loss of efficiency toward the end of a 2-hour exposure period, caused by unusually heavy (cumulative) deposition of PM on the virtual impactor slits. This situation occurred on days with unusually high ambient PM and high relative humidity and did not markedly influence the subjects’ overall exposure levels. In exposures with CAPs, the coefficient of variation of mass concentrations was approximately 20 percent. Nitrate, sulfate, elemental and organic carbon, and crustal elements (especially silicon, aluminum, and iron) were prominent components of CAPs. Organic carbon could not be quantified reliably because of measurement artifacts. Nitrate exposure concentrations covaried strongly with mass concentrations, but the other aforementioned components did not. That is, the relative proportions of sulfate, carbon, and crustal elements varied in different CAP exposures.
NO2 for exposure was generated from a compressed dilute mixture in inert gas. Thus, NO2 was more controllable than CAPs; its coefficient of variation across NO2 alone and NO2 + CAP exposures was 3 percent or less. In exposures to FA or CAPs alone, ambient NO2 was not actively filtered; the typical concentrations were 30-40 ppb. Because of logistical reasons, some subjects were exposed to FA and to CAPs alone (in a separate protocol) for several months before their exposures to NO2 and NO2 + CAPs. Thus, the order of exposures with and without NO2 was not completely randomized; exposures with NO2 occurred at a later date, on average, and more often in warm seasons.
Most respiratory responses, including symptom scores determined from standardized questionnaires, forced vital capacity, forced expired volume in 1 second, sputum total cell counts and differential cell counts, and sputum interleukin concentrations (IL-6, IL-8), showed no statistically significant variation attributable to separate or combined effects of CAPs and NO2. Maximal midexpiratory flow and arterial oxygen saturation (measured by fingertip pulse oximetry), however, showed small but statistically significant decrements associated with CAPs. These respiratory responses are consistent with dysfunction of relatively small peripheral airways. They were more noticeable in healthy than COPD subjects, contrary to our original expectation. This finding is plausible on the assumption that: (1) inhaled particles exert toxic effects at their site of deposition in peripheral airways; and (2) particles can penetrate to peripheral locations more readily through healthier airways. CAP exposure also was associated with decreased percentages of columnar epithelial cells in sputum. These results suggest that respiratory effects of the PM-NO2 mixture primarily may be PM-driven because co-exposure to NO2 did not enhance the responses significantly. Individual forced expiratory function responses tended to become more negative with increasing concentrations of sulfate in CAPs, suggesting that sulfate (or some other agent or closely associated with it) may be an important contributor to toxicity.
In healthy subjects, heart rate variability decreased slightly and the incidence of ectopic heartbeats increased slightly after CAP exposures. These effects were less noticeable after CAP + NO2 exposure. In COPD subjects, the corresponding exposure-related changes were in the opposite (possibly favorable) directions, although heart-rhythm status was less favorable overall. Most routine blood-count results did not change significantly in relation to exposures. CAPs + NO2, however, appeared to suppress increases in lymphocytes otherwise observable at 4 hours post exposure. Also, healthy subjects’ basophil counts increased after NO2 or CAPs alone (at different times), but not after the combined exposure. Blood biochemistry results showed no marked effect of experimental exposures on hemostasis. VonWillebrand factor, factor IX, and tissue plasminogen activator, however, showed significant variations attributable to exposures. Healthy subjects’ changes suggested a decreased tendency to clot formation, whereas COPD subjects’ responses suggested an increased tendency to both clot formation and fibrinolysis. Thus, hemostatic instability was the most marked extrapulmonary abnormality related to PM exposures in this study and is consistent with a generalized systemic inflammation.
In summary, this clinical study of elderly volunteers with and without COPD has demonstrated respiratory and systemic effects from relatively brief (2-hour) exposures to concentrated fine PM and a ubiquitous oxidant gas (NO2). The results suggest a primary PM effect even when combined with NO2. The specific etiological agent in the fine PM is unclear. The study also suggests that exposure effects may be as relevant in healthy elderly volunteers as in COPD patients. The evaluation of health effects from exposure to combined PM and gaseous pollutant(s) represents another relevant strategy to better understand the effects of particulate air pollution and warrants further investigation.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
|Other project views:||All 6 publications||2 publications in selected types||All 2 journal articles|
||Gong Jr. H, Linn WS, Terrell SL, Anderson KR, Clark KW, Sioutas C, Cascio WE, Alexis N, Devlin RB. Exposures of elderly volunteers with and without chronic obstructive pulmonary disease (COPD) to concentrated ambient fine particulate pollution. Inhalation Toxicology 2004;16(11-12):731-744.||
||Gong Jr. H, Linn WS, Clark KW, Anderson KR, Geller MD, Sioutas C. Respiratory responses to exposures with fine particulates and nitrogen dioxide in the elderly with and without COPD. Inhalation Toxicology 2005;17(3):123-132.||