1. Health Effects of Suspended Particulate Matter Judith C. Chow (Judy.Chow@dri.edu) John G. Watson Desert Research Institute Reno, Nevada, USA Presented at: The Workshop on Air Quality Management, Measurement, Modeling, and Health Effects University of Zagreb, Zagreb, Croatia 24 May 2007

2. Objectives Report progress for PM and health effects Explain ultrafine particles and their toxicological/ epidemiological associations Identify knowledge gaps and future challenges in PM research

3. Air Pollution/Health Issue http://www.epri.com/

4. Air Quality Decision Making Framework Emissions (rates, particle size, and composition) Transport and Transformation Concentrations in Air (composition, particle size, health indicator) Human Exposure (outdoor and indoor) Human Inhalation Dose to Target Tissues Adverse Health Effects National Research Council, 1998, Research Priorities for Airborne Particulate Matter: I - Immediate Priorities and a Long-Range Research Portfolio

5. National Research Council (NRC) Reports (1998, 1999, 2001, 2004)

6. History of Public Policy and PM Science SCIENCE 1930s-1950s Early Episode studies 1960s-1980s Ecological mortality and inhalation tox. studies 1989-mid 1990s New results from several epidemiologic studies U.S. PUBLIC POLICY 1955, 1963 Early national legislation 1967, 1970, 1971 Clean Air Act, amendments, NAAQS 1987 PM standards revised, TSP-PM 10 Pope and Dockery, 2006, JAWMA, 56(6)

7. History of Public Policy and PM Science (continued) SCIENCE 1997 Vedal’s “Lines that Divide” Growth in PM and health effects research (Vedal, 1997, JAWMA) 2006 “Lines that Connect” Gaps and skepticism (Pope and Dockery, 2006, JAWMA) U.S. PUBLIC POLICY 1997-2002 Promulgation of PM 2.5 standards, Legal challenges argued and largely resolved 2006 New proposed standards for PM 2.5 and PM 10-2.5 Pope and Dockery, 2006, JAWMA, 56(6)

8. Particle Size Distribution Watson, 2002, JAWMA, 52(6)

9. Inhalation Properties Chow, 1995, JAWMA 45(5); Phalen et al., 1991, Radiat. Protect. Dosim. 38(1/3) Lung deposition peaks at 40-60% for 30 nm UP Tracheal deposition is 20-40% for <10 nm UP

10. Potential Particulate Matter (PM) Health Indicators Ultrafine, fine, or coarse mass size fractions Mass, surface area, or number of particles Mass, sulfate, acidity, solubility, or transition metals Pollens, fungi, molds, or endotoxins Synergies with weather or other pollutants

11. 1997 A&WMA Critical Review and Discussion Summary

12. What is now no longer true from 1997 Critical Review? “… weak biological plausibility has been the single largest stumbling block to accepting the association as causal.” “… evidence supporting development of chronic illness from long-term particle exposure … is weak.” Vedal, 1997, JAWMA, 47(5)

13. Follow-up on PM and Health Effects Bates DV (2000). “Lines that connect: assessing the causality inference in the case of particulate pollution.” Environ Health Perspect 108:91-2. Pope CA III and Dockery DW (2006). “Health effects of fine particulate air pollution: lines that connect.”

14. 2006 Critical Review and Discussion Summary Pope and Dockery, 2006, JAWMA, 56(6); Chow et al., 2006, JAWMA, 56(10)

15. Key Aspects of 2006 Critical Review Short-term exposure and mortality Long-term exposure and mortality Time-scales of exposure Shape of concentration-response function Cardiovascular disease Biological plausibility Pope and Dockery, 2006, JAWMA, 56(6)

16. Recent Advances in PM Health Effects Short term exposure and mortality –>100 time series studies; single & multiple cities Long term exposure and mortality –Built around 6-City & ACS; growing prospective data base Time scales of exposure –Varied time scales; distributed lags Chow et al., 2006, JAWMA, 56(10)

17. Recent Advances in PM Health Effects (continued) Shape of the concentration response function –Lack of apparent threshold; near-linearity through ‘0’ Cardiovascular disease –Cardiac events; changes in function; progressive disease Biologic plausibility –Several prevailing theories – evidence for coherence with toxicology Chow et al., 2006, JAWMA, 56(10)

18. PM 10 O3O3 SO 2 CONO 2 Stieb et al., 2002, JAWMA, 52(4) Air Pollution Health Effects (Percent Excess Mortality)

19. Mortality risk in Harvard Six-City Study ( Cohort Follow-up) Steubenville Topeka Watertown Kingston St. Louis Portage Laden et al., 2006. Environ. Sci. Technol., 40(13)

20. *Associated with increments of 10 µg/m 3 PM 2.5 or 20 µg/m 3 PM 10 or British Smoke exposure Pope and Dockery, 2006, JAWMA, 56(6) Days of Exposure Mortality (%) Changes in Mortality Risk* in Exposure

21. Pope and Dockery, 2006, JAWMA, 56(6) Cardiovascular Mortality Risks* in long-term exposure Associated with increments of 10 µg/m 3 PM 2.5

22. Both fine and coarse PM induce health effects EPA ORD, 2004, PM Criteria Document

23. Particle composition changes with size (Fresno, CA, USA)

24. UP Decreases Rapidly with Distance from Roadways Reponen et al., 2003, J. Environ. Monit.

25. Health Effects of Ultrafine Particles (UP) The lag (in days) between concentration and effect CV: cardiovascular disease RE: respiratory disease (Ibald-Mulli et al., 2002, J. Aerosol Med., 15(2))

26. Hypotheses on Toxicological Effects of UP Inflammatory (i.e., large surface area, react with macrophages and epithelial cells) Not efficiently removed by macrophages Contain or release more toxic free radicals Inhibit phagocytosis (i.e., unable to remove foreign substances) Translocate from lung to other organs via bloodstream or lymphatic system Effects enhanced by oxidant gases (e.g., ozone) Effects are most severe on the elderly and people with compromised respiratory tracts (e.g., chronic obstructive pulmonary disease)

27. (Sorensen et al., 2003, Mutation Research 544 (2-3)) Conceptual Model of UP/PM and Health Effects (different pathways)

28. Hypothesis on Interactions between UP and Respiratory System (Donaldson et al., 2001, Occup. Environ. Med., 58(3))

29. Summary Much progress has been made regarding PM health effects Evidence of increasing cardiovascular effects in addition to pulmonary effects Better understanding of pathophysiological pathways to link PM-related mortality and morbidity Increasing research in the health effects of ultrafine particles

30. Knowledge Gaps Compliance air quality networks need to be designed for epidemiology studies. (Measurements at central site may not represent general population exposure.) Particle types and concentrations in toxicological studies are much higher and not representative of ambient air. Toxicological studies need to establish associations from animal subjects to humans.

31. Challenges Ahead Enhance air quality monitoring for research Assess toxicity of PM components Investigate health effects of long-term exposure to air pollutants Formulate multi-pollutant research programs Simmons et al., 2004, NRC

32. Challenges Ahead (continued) Integrate across disciplines –Design collaborative research –Prioritize funding to multidisciplinary teams –Encourage fellowships/sabbaticals –Conduct joint workshop/meeting and publish proceedings and peer-reviewed summaries Simmons et al., 2004, NRC