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Robert W. Clarke,¹ Brent Coull,² Ulrike Reinisch,¹ Paul Catalano,² Cheryl R. Killingsworth,¹ Petros Koutrakis,¹ Ilias Kavouras,¹ Gopala Gazula Krishna Murthy,¹ Joy Lawrence,¹ Eric Lovett,¹ J. Mikhail Wolfson,¹ Richard L. Verrier,³ and John J. Godleski¹

¹Department of Environmental Health; ²Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
³Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Abstract

Pulmonary inflammatory and hematologic responses of canines were studied after exposure to concentrated ambient particles (CAPs) using the Harvard ambient particle concentrator (HAPC) . For pulmonary inflammatory studies, normal dogs were exposed in pairs to either CAPs or filtered air (paired studies) for 6 hr/day on 3 consecutive days. For hematologic studies, dogs were exposed for 6 hr/day for 3 consecutive days with one receiving CAPs while the other was simultaneously exposed to filtered air ; crossover of exposure took place the following week (crossover studies) . Physicochemical characterization of CAPs exposure samples included measurements of particle mass, size distribution, and composition. No statistical differences in biologic responses were found when all CAPs and all sham exposures were compared. However, the variability in biologic response was considerably higher with CAPs exposure. Subsequent exploratory graphical analyses and mixed linear regression analyses suggested associations between CAPs constituents and biologic responses. Factor analysis was applied to the compositional data from paired and crossover experiments to determine elements consistently associated with each other in CAPs samples. In paired experiments, four factors were identified ; in crossover studies, a total of six factors were observed. Bronchoalveolar lavage (BAL) and hematologic data were regressed on the factor scores. Increased BAL neutrophil percentage, total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum/silicon factor. Increased circulating neutrophils and increased BAL macrophages were associated with the vanadium/nickel factor. Increased BAL neutrophils were associated with the bromine/lead factor when only the compositional data from the third day of CAPs exposure were used. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur factor. BAL or hematologic parameters were not associated with increases in total CAPs mass concentration. These data suggest that CAPs inhalation is associated with subtle alterations in pulmonary and systemic cell profiles, and specific components of CAPs may be responsible for these biologic responses. Key words: bronchoalveolar lavage, canines, environmental particles, hematology, inflammation. Environ Health Perspect 108:1179-1187 (2000) . [Online 15 November 2000]

http://ehpnet1.niehs.nih.gov/docs/2000/108p1179-1187clarke/ abstract.html

Address correspondence to R.W. Clarke, Room 2-223, 665 Huntington Avenue, Harvard School of Public Health, Boston, MA 02115 USA. Telephone: (617) 432-4354. Fax: (617) 432-0014. E-mail: Robert.Clarke@alkermes.com

We acknowledge contributions made by the following colleagues in the course of these studies: G. Allen, S. Ferguson, V. Hatch, M. Katler, E. Millet, T. Quon, C. Sioutas, R. Stearns, and J. Sullivan. We thank D. Dockery and P. Saldiva for editorial assistance.

This work was supported by NIH grants ES-08129, ES-00002, HL-07118, and HL-0176, as well as EPA Research Center Award R-827353 and grant 95-9 from the Health Effects Institute.

Received 14 December 1999 ; accepted 20 July 2000.