# Presentation: 761921

## Air Pollution Health Effects:What We Know and What We Think We Know

**Robert Devlin**
**Human Studies Division**
**Office of Research and Development**
**US EPA **

**2004 National Air Quality Conference**
**Baltimore, MD**
**February 2004**

## Slide 2

## A Brief History of PM

## The Houses of Parliament, Stormy Sky

**Claude Monet, 1904**

## Air Pollution Disasters

**1930  Meuse River Valley, Belgium**
**A three-day episode of severe air pollution makes 6,000 ill and kills 63.**

**1948 Denora, PA**
**Oct. 26 to 31: air pollution episode leaves 20 dead out of 14,000 persons.**

**1952 London, England**
**Dec. 4 to 9: “Killer Fog” leaves three to four thousand people dead.**

**London buses are escorted by lantern at 10:30 in the morning.**

**Donora, PA at noon on **
**Oct. 29, 1948**

## Mortality Attributed to the London Fog

**Schwartz, 1994**

## Acute Mortality Associated with Ambient PM Concentration

**Schwartz et al.,  1992**

## The National Morbidity, Mortality, and Air Pollution Study

**Samet et al.,  2000**

## Association Between Long Term Exposure to PM and  Mortality

**Harvard Six-Cities Adult Cohort**

- Purpose was to study the association between pulmonary changes and long term exposure to sulfates and sulfur dioxide
- Enrollment 1974 – 1977
- 		8,111 white men and women
- 		About 1,300 in each of six cities
- 		Age range 25 to 74 years
- Followed until 1991 (now 1999)
- 		14 to 17 years of follow-up
- 		111,076 person-years
- 		1,430 death

## Dockery et al., 1993

**Dockery et al., 1993**

## Why Were the Epidemiology Studies So Hard to Believe?

**Similar results were obtained from cities all around the world**
**But chemical composition differs geographically and temporally**
**PM levels are very low compared with other particle exposures **
**One cigarette = 10x more than a 24 hr exposure to PM**
**No widely accepted pathophysiological process or mechanism that could explain the epidemiology findings**

## Slide 12

## Current PM Health Effects Program

**In 1997 President Clinton stated:  “The EPA, in partnership with other Federal Agencies, will develop a greatly expanded coordinated interagency PM research program, which will contribute to understanding the science associated with PM health effects, as well as developing improved monitoring methods and cost-effective mitigation strategies.”**
**In 1998 Congress allocated substantial new funds for PM Research.**
**more than 250 million dollars in the past 6 years**
**At the same time it directed the EPA to arrange for an independent study by the National Research Council to develop priorities for a comprehensive PM Research Plan.**

## The NRC Reports

**The NRC Reports**

**The NRC has issued 3 reports which identify important research needs and recommend a multi-year portfolio of the highest priority research topics.**

## WHO Is Susceptible to PM?

HOW does PM cause adverse health effects? 

WHAT are the PM component(s) responsible for these effects?

**HOW**** ****does PM cause adverse health effects? **
**WHAT**** ****are the PM component(s) responsible for these effects?**

## WHO Is Susecptible to PM?

**Given: **
**200 natural deaths per day for a city of 8 million (e.g. Philadelphia)**
**Assume: **
**A 3-day PM episode raises the concentration from 30 to 80 ug/m****3**
**A relative risk of 1.05 per 50ug/m****3 ****change in PM Concentration**
**Result:**
**10**** extra deaths per day in Philadelphia**
** ****East Coast impact might be ~100 excess deaths**

**A Needle in A Haystack?**

## Cardiopulmonary disease appears to predispose to PM effects.

**Schwartz et al.,  1992**

## PM Can Trigger Myocardial Infarction

**772 MI patients who survived 24 hours **
**and completed interview **

**Peters et al,  2001**

**Watkinson et al., 1998**

**ECG Abnormalities and death rats exposed to PM**

## Other Populations May Also Be Susceptible to PM

**Zanobetti et al., 2002**

- Diabetics

- Infants

- 20% increase in pre-term births per 50 g increase in PM10
- Association between cardiac and aortic artery defects in new-borns and CO, levels

**Ritz  et al., 2002**

## PM May Cause Effects in Healthy People

**Devlin et al., 2003**

**Ghio et al., 2003**

## The Role of Genes in Susceptibility to Pollutants

**The environment pulls the trigger.**

**McDonnell et al., 1993**

**The extent of O****3 ****induced decrements in lung function varies by almost an order of magnitude in normal healthy subjects.  **
**Subjects brought back for a second exposure show the same degree of response, suggesting a genetic contribution to O****3**** responsiveness.  **

**The Role of Genes in Susceptibility to Pollutants**

## HOW Does PM Cause Adverse Health Effects?

**Traditionally, toxicologists have focused on respiratory tract responses to air pollutants**** **
**Ozone, NO****2****, SO****2**
**The association between PM and cardiovascular effects required a new approach to the study of air pollution**
**CV effects, vascular effects (clotting, endothelial cell dysfunction)**

**A New Kind of Challenge to Air Pollution Toxicologists**

## Ambient PM

**Pulmonary Reflexes**

**Sudden**
**Cardiac **
**Death**

**Autonomic Nervous**
**System**

**Cardiac Rhythm**

**BC/TC/VF**

**Heart Rate**

**Conduction/Repolarization**

**Pulmonary Inflammation**

**Systemic Inflammation**

**Endothelial**** ****Cell**
**Dysfunction**

**Platelet**
**Activation**

**Thrombosis**

**Plaque Rupture**

## Suwa et al. (2002)

- Exposure to PM collected from Ottowa caused a progression of atherosclerotic lesions towards a more advanced phenotype in hyperlipidemic rabbits.

- Seaton et al. (1999)
- Elevation in CRP associated with increase in PM; decrease in red blood cells (Aberdeen study)
- Peters et al. (2000)
- Elevation in CRP associated with increase in PM (MONICA study)

- Seaton et al. (1999)
- Aberdeen PM exposure associated with increased plasma fibrinogen, Factor VII
- Prescott et al. (2001)
- Edinburgh PM exposure associated with increased plasma fibrinogen

- Costa et al. (1997)
- Severe arrhythmias in monocrotaline treated rats exposed to ROFA
- Muggenburg et al. (2000)
- Slight bradycardia in dogs exposed to ROFA
- Watkinson et al. (2000)
- Increased arrthythmias in older rats exposed to PM collected in Ottowa

## Direct Cardiac Injury in Rats Exposed to PM

**PM-exposed 40X**

**Air-exposed 40X**

**Rats exposed to ambient PM – 1 d/wk/16 wks  **

**Kodavanti et al., 2003**

## Deposition and Clearance of Inhaled Particles

**Kim  et al., 1997**

**0**

**0.05**

**0.1**

**0.15**

**0.2**

**0.25**

**0.3**

**Normal**

**Smokers**

**SAD**

**Asth**

**COPD**

**Dp = 1 um**

## WHAT Are the PM Component(s) Responsible for These Effects?

## PM Is a Very Complex Pollutant

## Geneva Steel Mill:  The Utah Valley

## Metals Present in UV PM Can Cause Lung Inflammation and Injury

**Ghio et al., 2001**

**Molineri et al., 2002**

**Removal of metals eliminates inflammation**

**Instillation of UV PM into Human Lungs**

## Slide 31

## Can We Link PM Effects with Specific Sources of Pollution?

**% Increase in Daily Deaths**

**Laden et al., 2000**

**Speciation monitoring of airsheds of differing composition may enable identification of components, and sources of those components, that contribute to adverse health outcomes  **

## Cardiovascular Effects Associated with PM Derived from Mobile Sources

**Cardiovascular Effects Associated with PM Derived from Mobile Sources**

**Riediker et al., 2004**

## Will It Matter if Air Pollution Decreases? 

**Table 3. Change in age-standardized total, cause-specific, and age-specific mortality rates for Dublin County Borough for 72 months before and after ban of sale of coal in Dublin **

**Clancy et al,  2002**

**Will It Matter if Air Pollution Decreases? **

**The Dublin Experience**

**Dublin’s air quality deteriorated in the 1980s after a switch from oil to cheaper bituminous coal for heating.**
**In 1990 the Irish Government banned the use of bituminous coal within the city of Dublin, resulting in a reduction in PM concentrations. **

## The Utah Valley

## EPA’s Goal for Clean Air

**EPA’s Goal for Clean Air**