Anthony J. DeLucia, Ph.D.

Anthony J. DeLucia, Ph.D.

Chair

William M. Voigt

Chair-elect

Judge Cordell D. Meeks, Jr.

Past-Chair

Charles M. Heinrich

Vice-Chair

October 11, 2002

Imajean Heatherington, CPA

Secretary

James M. Anderson

Treasurer

John L. Kirkwood

President &

Chief Executive Officer

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Annotated Bibliography of Recent Studies on the

Health Effects of Air Pollution

In the last year, hundreds of scientific papers on the health effects of air

pollution have been published reporting on effects ranging from respiratory

symptoms to premature mortality. The studies extend our understanding of

the short- and long-term effects of exposure to common air pollutants,

provide new information on potential cardiovascular mechanisms, and

identify especially susceptible populations, including children.

This bibliography represents a small sampling of studies published from

mid-2001 to mid-2002 in peer-reviewed journals. The new studies link air

pollution with lung cancer, heart attacks, strokes, high blood pressure,

congenital heart defects, asthma, and even brain damage. They identify

diabetics, asthma patients, those with congestive heart failure, and children

who play outdoors as being at increased risk. The recent research

elucidates several pathways to explain the effects of air pollution on the

cardiovascular system.

www.lungusa.org

This bibliography does not attempt to be comprehensive: exclusion does

not imply that a study is unimportant; inclusion does not imply

endorsement.

LONG-TERM MORTALITY STUDIES

When You Can’t

Breathe, Nothing

Else Matters®

For nearly 100 years, the

American Lung Association,

Lung Association affiliates

Throughout the United States and

the American Thoracic Society

have worked together in the fight

against lung disease.

European Long Term Cohort Study Confirms PM-Mortality Link

A study published by The Lancet concludes that "long-term exposure to

traffic-related air pollution may shorten life expectancy."

Dutch researchers studied 5,000 people in the Netherlands from 1986 to

1994 that were participants in a prospective cohort study on diet and cancer.

They found that people living near major roads with higher concentrations

of black smoke were at increased risk of premature death from

cardiopulmonary causes.

1

The researchers note that traffic emissions contain many pollutants that might be

responsible for the mortality association, including ultrafine particles, diesel soot and

nitrogen oxides, though they added that nitrogen dioxide is unlikely to cause death.

"The specificity of the association and the consistency with chronic morbidity studies,

adds to the plausibility of traffic-related air pollution effects," conclude the researchers.

The study is significant because it confirms the Harvard Six Cities Study and the

American Cancer Society study which linked long-term exposure to particulate air

pollution to premature death in the U.S.

Hoek, G., Brunekreef, B., Goldbohm, S., Fischer, P., van den Brandt, P. A. Association Between Mortality

and Indicators of Traffic-Related Air Pollution in the Netherlands: A Cohort Study, The Lancet, Vol. 19,

pp. 1203-1209, 2002.

Research Links Air Pollution to Lung Cancer

Prolonged exposure to fine particulate air pollution significantly increases the risk of

dying from lung cancer and cardiopulmonary causes, according to a new study of

500,000 adults in over 100 American cities.

The new study extended the follow-up period for participants in the study of the

American Cancer Society cohort from seven to 16 years, and looked at recent fine

particle monitoring information for the years 1999-2000. Importantly, investigators

reported that prevailing levels of PM2.5 in the U.S. are associated with significant health

risks.

Authors concluded that: "the findings of this study provide the strongest evidence to date

that long term exposure to fine particulate air pollution common to many U.S. cities is an

important risk factor for cardiopulmonary disease mortality. In addition, the large

cohort and extended follow-up have provided an unprecedented opportunity to evaluate

associations between air pollution and lung cancer mortality. Elevated fine particulate

air pollution exposures were associated with significant increases in lung cancer

mortality. Although potential effects of other unaccounted for factors cannot be excluded

with certainty, the associations between fine particulate air pollution and lung cancer

mortality as well as cardiopulmonary mortality are observed even after controlling for

cigarette smoking, body mass, diet, occupational exposure, numerous other individual

risk factors, and after using recent advances in statistical modeling to control for

regional and other spatial differences."

Pope, C.A., Burnett, R.T., Thun, M.J., Calle, E.E., Krewski, D., Ito, K., and Thurston, G.D. Lung Cancer,

Cardiopulmonary Mortality, and Long-term Exposure to Fine Particulate Air Pollution, Journal of the

American Medical Association, Vol. 287, No. 9, March 6, 2002.

2

Mortality Risk Analyses Should be Based on Long-Term Studies

A debate has raged in the public policy arena about whether to use the short-term or the

long-term epidemiological studies to estimate the risks of premature mortality attributable

to particulate air pollution. A study by Knzli et al. presents a conceptual model for the

interpretation of these studies, which shows that short-term time-series and long-term

cohort studies address different aspects of the association between air pollution and

death. Time-series studies capture only cases in which death has been triggered by air

pollution exposures that occur shortly before death, while cohort studies capture all air

pollution-related categories of death, including deaths of persons whose underlying

health condition leads to premature death, without being related to the level of pollution

shortly before death.

For these reasons, the authors conclude “that time-series analyses underestimate cases of

death attributable to air pollution and that assessment of the impact of air pollution on

mortality should be based on cohort studies.”

The National Academy of Sciences recently issued a report on “Estimating the Public

Health Benefits of Proposed Air Pollution Regulations.” Importantly, the report

concluded that EPA has appropriately based their estimates of morality on long-term

cohort studies, which give “a more complete assessment because they include long-term,

cumulative effects of air pollution.” In particular, the report concluded that EPA’s use of

the American Cancer Society (ACS) study for the evaluation of PM-related premature

mortality was reasonable, given the size and precision of the study.

Knzli, N., Medina, S., Kaiser, R., Qunel, P., Horak, F., Jr., and Studnicka, M. Assessment of Deaths

Attributable to Air Pollution: Should We Use Risk Estimates Based on Time Series or on Cohort Studies?

Am. J. Epidemiol. 2001;153:1050-5.

National Research Council, Committee on Estimating the Health-Risk-Reduction Benefits of Proposed Air

Pollution Regulations, “Estimating the Public Health Benefits of Proposed Air Pollution Regulations,”

National Academies Press, 2002.

SHORT-TERM MORTALITY STUDIES

Strong Evidence for PM-Mortality Relationship Persists in Updated Study

In May 2002, researchers reported an error in the default assumptions in the software

used to analyze the National Morbidity, Mortality and Air Pollution Study (NMMAPS).

The researchers concluded that a refined analysis changes the quantitative estimates of

risk, but the major conclusions remain the same. The three important conclusions of the

study remain unchanged by the re-analysis: strong evidence of an association between

acute exposure to particulate air pollution (PM10) and daily mortality; the association is

strongest for respiratory and cardiovascular causes of death; the association can not be

attributed to other pollutants including NO2, CO, SO2 or O3, nor to weather.

3

The software error does affect all time series studies of air pollution, but only certain

recent studies with two or more smooth curves in the generalized additive model

(GAM).

Further, the reported error has no affect on the results of the landmark long-term studies

of particles, the Harvard Six Cities Study and the American Cancer Society study both of

which were reanalyzed in depth and upheld in 2000. These studies found that prolonged

exposure to particulate air pollution significantly increases the risk of dying from

cardiopulmonary causes.

Importantly, the long-term studies provide the basis for the large risk estimates

associated with particulate air pollution, so these estimates remain unchanged by recent

developments.

Researchers conclude that “… there was strong evidence for a positive association

between acute exposure to PM10 and death, even with very conservative adjustments for

trend, seasonality, and weather.”

Dominici, F., McDermott, A., Zeger, S.L. and Samet, J.M. On the Use of Generalized Additive Models in

Time-Series Studies of Air Pollution and Health, Am. J. Epidemiol., Vol. 156, No. 3, pp 193-203, August

1, 2002.

“Harvesting” Theory Disproven

Some have argued that the short-term increases in mortality associated with air pollution

represent a “harvesting” effect, that is, the advancement of death by a few days in very

frail people. This theory of mortality displacement has been dispelled by analyses of

single-city mortality studies. Two recent studies have strengthened this conclusion by reexamining multi-city data sets in the U.S. and in Europe.

Researchers from Johns Hopkins University conducted an analysis of daily mortality,

particulate air pollution, and weather in Pittsburgh, PA, Minneapolis, MN, Seattle,

WA, and Chicago, IL.

Researchers found larger relative risks of mortality associated with particulate air

pollution for periods of 1 to 2 months, compared to shorter periods of 1 to 4 days.

They conclude: “These analyses provide additional evidence that associations of particle

indexes and mortality do not imply only an advance in the timing of death by a few days

for frail individuals.”

Another study examined this issue in the context of the multi-city “Air Pollution and

Health: A European Approach” (APHEA-2) study. The study showed that the effect size

estimate for airborne particles more than doubled when long-term effects, up to 40 days,

were considered.

4

Researchers reported, “ our study confirms that the effects observed in daily time-series

studies are not due primarily to short-term mortality displacement.” They also report

that, “risk assessment based on short-term associations likely underestimate the number

of early deaths that are advanced by a significant amount, and that estimates based on

the cohort studies, or studies such as this one, would more accurately assess the public

health impact.“

Dominici, F., McDermott, A., Zeger S.L., and Samet, J. Airborne Particulate Matter and Mortality: TimeScale Effects in Four U.S. Cities. American Journal of Epidemiology, In press.

Zanobetti, A., Schwarz, J., Samoli, E., Gryparis, A., Touloumi, G., Atkinson, R., Le Tertre, A., Bobros, J.,

Celko, M., Goren, A., Forsberg, B., Michelozzi, P., Rabczenko, D., Aranguez Ruiz, E., and Katsouyanni,

K. The Temporal Pattern of Mortality Responses to Air Pollution: A Multicity Assessment of Mortality

Displacement. Epidemiology, Vol. 13, pp. 87-93, 2002.

Air-Conditioning May Account for Regional Differences in Risk Estimates

Studies of acute effects of particulate matter air pollution show variability in the

exposure-response relationships between cities. This study explored whether differences

in the prevalence of air conditioning and different sources of PM could partially explain

the regional heterogeneity.

The study examined data from a study of hospital admissions for cardiovascular and

respiratory causes in 14 U.S. cities, data on air conditioning from a 1993 American

Housing Survey, and data on PM10 emissions source categories, vehicle miles traveled,

and population density from U.S. EPA.

Investigators concluded: “the results suggest that air conditioning and proportion of

especially traffic-related particles significantly modify the effect of PM10 on hospital

admissions, especially for cardiovascular disease.”

Janssen, N.A.H., Schwartz, J., Zanobetti, A., and Suh, H.H. Air Conditioning and Source-Specific Particles

as Modifiers of the Effect of PM10 on Hospital Admissions for Heart and Lung Disease. Environ. Health

Perspect. Vol. 110, pp. 43-49, 2002.

SUSCEPTIBLE POPULATIONS

Airborne Particles Increase the Risk of Heart Disease in Diabetics

Particulate air pollution has been associated with decreased heart rate variability,

increased clotting risk factors, and increases in systemic markers of inflammation.

Diabetes is a disease characterized by disturbances in all of these cardiovascular risk

factors. Researchers hypothesized that since particles and diabetes may affect some of

the same pathways, they may interact to increase the risk of cardiovascular disease.

5

The study examined Medicare data for hospital admissions for heart disease among the

elderly in Cook, County (Chicago), IL. Investigators found that people with diabetes

had twice the PM10-associated risk for heart disease as nondiabetics, and concluded that

diabetics are a susceptible population. A follow-up study in Chicago, IL, Detroit, MI,

Pittsburgh, PA, and Seattle, WA came to similar conclusions.

These findings have important public health implications because more than 5 percent of

the U.S. population has been diagnosed with diabetes, and an additional 2.7 percent have

undiagnosed diabetes.

Zanobetti, A., and Schwartz, J. Are Diabetics More Susceptible to the Health Effects of Airborne Particles?

Am. J. Respir. Crit. Care Med. Vol. 164. pp. 831-833, 2001.

Zanobetti, A., Schwartz, J. Cardiovascular Damage by Airborne Particles: Are Diabetics More

Susceptible? Epidemiology, Vol. 13, No. 5, pp. 588-592, Sept. 2002.

PM10 and Ozone Have Strong, Immediate Link with Stroke Deaths

Air pollution may play a part in the causation of strokes, one of the leading causes of

death and long-term disability, according to a team of researchers from four research

centers in Korea and the Harvard School of Public Health. The findings are based on

data from Seoul, Korea, a city with relatively high PM concentrations and high numbers

of fatal strokes.

Researchers reported that rises in PM10 and ozone concentrations had a strong, nearly

immediate link with stroke deaths. Stroke mortality also increased in association with

NO2, SO2 and carbon monoxide concentrations. The effects persisted after controlling

for potential confounding factors such as weather and season. Researchers conclude

“that PM10 and gaseous pollutants are significant risk factors for acute stroke death and

that the elderly and women are more susceptible to the effect of particulate pollutants.”

A seven-year follow-up study in Seoul examined daily stroke deaths in relation to air

pollution. After controlling for influences such as temperature, relative humidity, and

atmospheric pressure, researchers observed a statistically significant relationship between

same day concentrations of total suspended particulates and sulfur dioxide, and death

from ischemic strokes. Ischemic strokes, the most common type of strokes, occur when a

blood clot or narrowed artery cuts off blood supply to the brain.

Hong, Y.-C., Lee J.-T., Kim, H., Ha, E.-H., Schwartz, J., and Christiani, D.C. Effects of Air Pollutants on

Acute Stroke Mortality. Environ. Health Perspec. Vol. 110, pp. 187-191, 2002.

Hong, Y.-C., Lee, J.-T., Kim, H., Kwon, H.-J., Air Pollution: A New Risk Factor in Ischemic Stroke

Mortality, Stroke, Vol. 33, No. 9, pp. 2165.

6

PM10 and Ozone Air Pollution Worsens the Health of Adults with Severe Asthma

Very few panel studies of adults with severe or moderately severe asthma have been

conducted. Most previous studies have been of children. Desquoroux and colleagues

designed a study with stringent criteria for inclusion, rigorous medical surveillance, and a

long period of observation.

Sixty adult patients with severe asthma and receiving medical treatment were followed by

their physicians in Paris, France for a period of 13 months. Daily levels of SO2, PM10,

NO2, and ozone were provided by the air quality monitoring network.

Increases in PM10 were associated with an increase in the incidence of asthma attacks 3-5

days later. The delayed effect of PM is consistent with impacts on inflammatory

mechanisms.

Increases in the maximum 1-hour ozone level were associated with increased asthma

attacks among allergic patients, after 2 days. The results suggest that weak

concentrations of ozone may increase bronchial reactivity with allergens in allergic

asthma patients.

“The results of our study suggest that ambient Paris levels of PM10 and O3 affected

health of severe asthmatics, despite their treatment,” report the study authors.

Desqueroux, H., Pujet, J.-C., Prosper, M., Squinazi, F., Momas, I. Short-Term Effects of Low-Level Air

Pollution on Respiratory Health of Adults Suffering from Moderate to Severe Asthma. Environmental

Research Section A, Vol. 89, pp. 29-37, 2002.

Nitrogen Dioxide and Ozone Increase the Risk of Death in Patients with Severe

Asthma

A study of 1,000 patients over 14 years old in Barcelona, Spain was conducted to assess

the relationship between acute exposure to air pollution, pollen, and mold spores in a

cohort of patients that had previously been admitted to an emergency room for an asthma

exacerbation. Records were evaluated to determine which of these patients died during

the period from 1985-1995. Air pollution, pollen, and spore levels were measured a city

monitoring station.

Researchers found that asthmatic patients with a history of more than one emergency

room admission for asthma had an increased risk of dying on days with high nitrogen

dioxide concentrations. High ozone days during the spring and summer also increased

the risk of death in patients with severe asthma. The association with particles, pollen

and spores was not significant.

“Nitrogen dioxide and ozone may exacerbate severe asthma and even cause death among

asthmatic subjects,” reported the researchers.

7

Sunyer, J., Basagana, X., Belmonte, J., and Anto, J.M. Effect of Nitrogen Dioxide and Ozone on the Risk

of Dying in Patients with Severe Asthma. Thorax, Vol. 57, No. 8, pp. 687-693, August, 2002.

Air Pollution Exerts Greater Mortality Impact in Patients with Congestive Heart

Failure

This study examined the short-term association between a variety of air pollutants and

mortality among patients with congestive heart failure in Seoul, Korea.

“… It seems clear that air pollution in Seoul was related to an increased daily mortality

and that congestive heart failure patients were particularly susceptible,” conclude the

researchers, strengthening the case that an important mechanism of air pollution effect

involves the cardiovascular system.

Kwon, H.-J., Cho, S.-H., Nyberg, F., and Pershagen, G. Effects of Ambient Air Pollution on Daily

Mortality in a Cohort of Patients with Congestive Heart Failure. Epidemiology, Vol. 12, pp. 413-419, 2001.

Sensitive Individuals are Highly Susceptible to Airborne Particles

"Part of the explanation for the persistent epidemiological findings of associations

between mortality and morbidity with relatively modest ambient exposures to airborne

particles may be that some people are much more susceptible to particle-induced

responses than others," write Professor Dale Hattis of Clark University, and coauthors.

This study relied on an analysis of studies of human systemic responses to dust and other

agents that induce acute changes in lung function to quantitatively explore variability

among individuals in breathing rates and deposition to the deep lung.

The study found that 99.9th percentile individuals respond to doses of particles 150 to

450 times smaller than are needed to affect average people.

Hattis D, Russ A, Goble R, Banati P, Chu M., Human Interindividual Variability in Susceptibility to

Airborne Particles. Risk Analysis, Vol. 4, pp. 585-599, August, 2001.

EFFECTS ON CHILDREN

Ozone and Carbon Monoxide Linked to Cardiac Birth Defects

Women in Southern California who are exposed to high concentrations of ozone and

carbon monoxide may be at increased risk of giving birth to babies with serious heart

defects, including holes in the heart, arterial defects, or pervasively malformed hearts,

according to a study by UCLA researchers.

California maintains a registry of birth defects. The study correlated motor vehicle

related air quality data with information on more than 9,000 babies born between 1990

8

and 1993 in Los Angeles, Riverside, San Bernardino, and Orange counties.

Researchers calculated average monthly pollution exposure estimates for each pregnancy

in the study.

Risk of holes in the heart increased in a dose-response fashion with increasing secondmonth carbon monoxide exposure. The second month of pregnancy is a critical period

for fetal heart development. In addition, second-month ozone exposure increased the risk

of aortic artery and valve defects.

Researchers concluded, “…our results substantially extend the epidemiologic data on the

potential relation between increases in ambient air pollutants during vulnerable

pregnancy periods and congenital malformations.”

Ritz, B., Yu, F., Fruin, S., Chapa, G., Shaw, G.M. and Harris, J.A. Ambient Air Pollution and Risk of Birth

Defects in Southern California. Am. J. Epidemiol. Vol.155, No. 1, pp. 17-25, 2002.

Particle Pollution Retards Lung Function Growth In Teenagers, Akin to Smoking

A study of California teenagers has found that PM10 air pollution retards lung function

growth as much as smoking.

Researchers studied 110 children who had moved from communities that are part of the

California Children's Health Study to determine whether changes in air quality caused by

relocation were associated with changes in annual lung function growth rates.

Researchers found that changes in PM10 exposure during adolescent growth years have a

"measurable and potentially important effect on lung function growth and performance."

Reductions in annual respiratory growth rates during adolescence may be a significant

predictor of respiratory health in later life.

The reductions observed "suggest that ambient air pollution exposure has a similar

magnitude of effect on lung function development to that previously observed for children

who are active smokers," reports the study.

"The results of this study, together with those of the numerous previously reported

investigations of PM10 and its association with increased morbidity and mortality,

underscore the national concern about particulate exposure and its relation to public

health," researchers conclude.

Another study followed 1,600 Southern California children enrolled as fourth graders in

1996 for four years. Significant deficits in lung function growth rate were associated

with exposure to acid vapor, NO2, PM2.5, and elemental carbon. Exposure to ozone was

correlated with reduced growth in peak flow rate. Larger deficits in lung function growth

rate were observed in children who spent more time playing outdoors, confirming

findings from an earlier study of another similar cohort. The results “provide further

9

evidence that ambient levels of air pollution in southern California have a detrimental

effect on lung function growth in children” conclude the authors.

Avol, E.L., Gauderman, W.J., Tan, S.M., London, S.J., and Peters, J.M. Respiratory Effects of Relocating

to Areas of Differing Air Pollution Levels. Am. J. Respir. Crit. Care Med. Vol 164, pp. 2067-2072, 2001.

Gauderman, W.J., Gilliland, G.F., Vora,H., Avol, E., Stram, D., McConnell, R., Thomas, D., Lurmann, F.,

Margolis, H.G., Rappaport, E.B., Berhane, K., and Peters, J.M. Association between Air Pollution and

Lung Function Growth in Southern California Children: Results from a Second Cohort. Am. J. Respir.

Crit.Care Med. Vol. 166, pp. 76-84, 2002.

Air Pollution Stunts Lung Function Growth in School Children

Researchers in Austria have followed almost a thousand school children from 8

communities for 3 years, with lung function measurements taken in the winter and

summer. Higher summertime PM10 concentrations were associated with a slower

increase in FEV1 (forced expiratory volume in one second), a proxy for large airways’

growth, and with another lung function measure intended to reflect the growth of small

airways.

Exposure to NO2 and ozone also reduced lung-function growth, confirming earlier work.

The authors conclude, “…the present study provided further evidence for a long-term

effect of particulate matter <10 m in diameter on the development of pulmonary

function in elementary schoolchildren. Early impairment of lung-function growth could

lead to lower lung-function parameters in adulthood, predisposing to chronic pulmonary

diseases.”

Horak, F., Jr., Studnicka, M., Gartner, C., Spengler, J.D., Tauber, E., Urbanek, R., Veiter, A., Frischer, T.

Particulate Matter and Lung Function Growth in Children: A 3-yr Follow-up Study in Austrian

Schoolchildren. Eur. Respir. J., Vol. 19, pp. 838-845, 2002.

Inner City Children with Asthma Experience Respiratory Symptoms and Decreased

Lung Function in Relation to Air Pollution

The effect of daily ambient air pollution was studied in a cohort of 850 asthmatic children

ages 4-9 living in eight inner city urban areas in the U.S. The urban areas studied were

Bronx and East Harlem, NY, Baltimore, MD, Washington, DC, Detroit, MI,

Cleveland, OH, Chicago, IL and St. Louis, MO.

The impact of pollution developed over several days, with the largest effects seen in

morning measurements of lung function. NO2, SO2, and PM10 were associated with an

increase in morning asthma symptoms, with NO2 exhibiting the strongest influence.

Ozone exhibited the greatest effect on peak expiratory flow rate. Adverse respiratory

effects were reported in all the cities studied.

10

Researchers conclude: “this longitudinal analysis supports previous time-series findings

that at levels below current USA air-quality standards, summer-air pollution is

significantly related to symptoms and decreased pulmonary function among children with

asthma.”

Mortimer, K.M., Neas, L.M., Dockery, D.W., Redline, S., Tager, I.B. The Effect of Air Pollution on InnerCity Children with Asthma, Eur. Respir. J. Vol. 19, pp. 699-705, 2002.

Truck Traffic Contributes to Childhood Asthma Hospitalizations

A study in Erie County, New York (excluding the city of Buffalo) has shown that

children living in neighborhoods with heavy truck or trailer traffic within 200 meters of

their homes had increased risks of asthma hospitalization. The study examined hospital

admission for asthma amongst children ages 0-14, and residential proximity to roads with

heavy traffic.

Lin, S., Munsie, J.P., Hwang, S.-A., Fitzgerald, E., and Cayo, M.R. Childhood Asthma Hospitalization and

Residential Exposure to State Route Traffic. Environmental Research, Section A, Vol. 88, pp. 73-81, 2002.

Coarse Particles (PM10-2.5) Associated with Asthma Hospitalization Among Children

This study used two analytical techniques to assess associations between different size

fractions of particulate matter and asthma hospitalization among children ages 6-12 living

in Toronto, Canada between 1981 and 1993.

The researchers found a stronger effect of coarse particles (PM10-2.5) on asthma

hospitalization compared with both PM2.5 and PM10, using both analytical techniques.

The stronger effect of PM10-2.5 persisted, even after adjusting for the effects of gaseous air

pollutants.

There are few studies of the coarse particle fraction, and they are of particular interest

because U.S. EPA will likely establish a new standard for coarse particles.

Lin, M., Chen, Y, Burnett, R.T., Villeneuve, P.J., and Krewski, D. The Influence of Ambient Coarse

Particulate Matter on Asthma Hospitalization in Children: Case-Crossover and Time-Series Analyses.

Environ. Health Perspect. Vol. 110, pp. 575-581, 2002.

Decreases in Air Pollution Shown to Improve Children’s Health

The reduction in SO2 and total suspended particulate levels in eastern Germany following

reunification provides a natural experiment to assess associated improvements in human

health. This study sought to examine the effect of the decline in air pollution due to a

reduction in coal combustion on elementary school children’s symptoms of bronchitis.

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Researchers conclude, “the prevalence of nonasthmatic respiratory disorders may be

reduced within a short time period by improving air quality. Our data on long-term

exposures to air pollution indicate the reversibility of adverse health effects in children

and add further evidence of a causal association with combustion-related air pollutants.”

Heinrich, J., Hoelscher, B., Frye, C., Meyer, I., Pitz, M., Cyrys, J., Wjst, M., Neas, L., and Wichmann, H.E. Improved Air Quality in Reunified Germany and Decreases in Respiratory Symptoms. Epidemiology,

Vol. 13, pp. 394-401, 2002.

BIOLOGIC MECHANISMS AND CARDIAC EFFECTS

Breathing Smog Causes Blood Vessels to Constrict

A chamber study on healthy human volunteers has demonstrated that breathing ozone and

particulate matter for only two hours, at levels typical of a polluted day in Los Angeles,

causes a major artery in the arm to constrict significantly.

Scientists observed that breathing air pollutants caused an immediate constriction of 2 to

4 percent in the blood vessel in the arm. Although this is unlikely to harm a healthy

person in the short term, it could impact those with existing heart disease or circulatory

problems, and could possibly trigger a heart attack, according to researchers.

The authors concluded, "This finding is important because … it provides evidence that

the observations shown by large epidemiological studies are biologically plausible."

Brook, R.D., Brook, J.R., Urch, B., Vincent, R., Rajagopalan, S., and Silverman, F. Inhalation of Fine

Particulate Air Pollution and Ozone Causes Acute Arterial Vasoconstriction in Healthy Adults. Circulation,

Vol. 105, pp. 1534-1536, 2002.

PM10 Provokes Inflammatory Response in Laboratory Animals, in Human Lung

Cells In Vitro, and in Humans

Scientists have found that inhalation of urban particles will increase the blood levels of

endothelins, potent vasoconstrictors which can increase blood pressure and contribute to

congestive heart failure. A study in laboratory rats found that exposure to urban

particulate matter (PM) increased endothelin levels, and also caused an increase in blood

pressure. The researchers found that particles can cause rapid (2 hours) and sustained (24

hours) systemic cardiovascular changes, without a requirement for acute lung injury.

In another study, researchers hypothesized that following PM10 exposure, cytokines,

proteins produced in the lung, are released into the blood, inducing a systemic

inflammatory response, which plays a role in cardiopulmonary effects. This study

exposed cultured human bronchial epithelial cells to ambient particulate matter obtained

from air filters in Ottawa, Canada. Researchers found that concentrations of various

proteins produced increased in a dose-dependent manner. They concluded that “primary

human bronchial epithelial cells exposed to ambient PM10 produce proinflammatory

12

mediators that contribute to the local and systemic inflammatory response, and we

speculate that these mediators may have a role in the pathogenesis of cardiopulmonary

disease associated with particulate air pollution.”

A third study measured cytokines in the circulation of healthy young army cadets in

Singapore exposed to air pollution during the 1997 Southeast Asian forest fires.

Vincent, R., Kumarathasan, P., Goegan, P., Bjarnason, S.G., Gunette, J., Brub, D., Adamson, I.Y.,

Desjardins, S., Burnett, R.T., Miller, F.J., and Battistini, B. Inhalation Toxicology of Urban Ambient

Particulate Matter, Acute Cardiovascular Effects in Rats. Health Effects Institute, Research Report 104,

2001.

Fujii, T., Hayashi, S., Hogg, J.C., Vincent, R., and Van Eeden, S.F. Particulate Matter Induces Cytokine

Expression In Human Bronchial Epithelial Cells. Am. J. Respir. Cell Mol. Biol. Vol. 25, pp. 265-271,

2001.

Van Eeden, S.F., Tan, W.C., Suwa, T., Mukae, H., Terashima, T., Fujii, T., Qui, D., Vincent, R., and Hogg,

J.C. Cytokines involved in the Systemic Inflammatory Response Induced by Exposure to Particulate Matter

Air Pollutants (PM10), Am. J. Respir. Crit. Care Med. Vol. 164. pp. 826-830, 2001.

Inhaled Ultrafine Particles Pass into the Bloodstream

With the aid of a radioisotope enhanced imaging technique, researchers in Belgium have

shown that ultrafine particles can enter a person’s bloodstream from the lungs. This

study of human volunteers was intended to investigate whether the smallest particles can

move from the lungs into the circulation, where they might have a direct effect on

cardiovascular endpoints.

Alternative hypotheses hold that particles produce pulmonary inflammation with a

systemic release of cytokines, which may influence cardiovascular endpoints.

Alternately, it has also been proposed that pollutants may cause alterations in cardiac

autonomic function thus causing changes in heart rate variability and increasing the risk

of sudden cardiac death.

The investigators conclude that “…we are confident that our findings provide plausible

evidence for particle translocation from the lung into the blood and then its distribution

to the organs,” and that this process could account for cardiovascular illness and death

related to ambient particle pollution.

Nenmar, A., Hoet, P.H.M., Vanquickenborne, B., Dinsdale, D., Thomeer, M., Hoylaerts, M.F., Vanbillioen,

H., Mortelmans, L., Nemery, B., Passage of Inhaled Particles in to the Blood Circulation in Humans.

Circulation, Vol. 105, pp. 411-414, 2002.

PM Accelerates and Aggravates Artery Disease

A study of laboratory rabbits found that atherosclerosis, a disease marked by cholesterollipid-calcium deposits in the walls of the arteries, was accelerated by exposure to PM10,

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compared to rabbits exposed to clean air. Athererosclerosis is the leading cause of

disease and death in Western societies. The study also found that pollution exposure

increased susceptibility to plaque rupture, which can trigger heart attacks.

“Progression of atherosclerosis and increased vulnerability to plaque rupture may

underlie the relationship between particulate air pollution and excess cardiovascular

death,” concluded the investigators.

Suwa, T., Hogg, J.C., Quinlan K.B., Ohgami, A., Vincent, R., van Eeden, S.F. Particulate Air Pollution

Induces Progression of Atherosclerosis. J. Am Coll. Cardiol. Vol. 39, pp. 943-945, March 20, 2002.

Healthy Workers Exposed to PM2.5 Experience Reduction in Heart Rate Variability

Decreased heart rate variability is an indicator of the diminished ability of the heart to

respond to stress, and is a risk factor for mortality from cardiovascular disease.

This is the first study to examine the effects of PM2.5 on a younger population, by

incorporating continuous personal monitoring in an occupational setting.

The study population was relatively young boilermaker construction workers

occupationally exposed to residual oil fly ash and metal fumes. Continuous monitoring

of PM2.5 exposure took place during and away from work. Statistically significant

decreased heart rate variability was observed in association with 1-hour average PM2.5

concentrations. The effect on heart rate variability was smaller than has been reported in

elderly populations.

The findings suggest “a relatively rapid-acting component in the mechanism of action of

PM2.5 on heart rate variability changes,” according to the researchers.

A follow-up study by the same group of researchers at the Harvard School of Public

Health explored the effect of specific metallic components of PM2.5 on the cardiac

function of boilermakers. The effect of six metals – vanadium, nickel, chromium, lead,

copper and manganese – on heart rate and heart rate variability were examined.

Measurements were collected by a portable electrocardiogram monitor and a personal

monitor of airborne concentrations. After adjusting for age, baseline heart rate, and

smoking status, small changes in heart rate were seen for all the metals, suggesting an

association between airborne metals and significant alteration in heart function.

Magari, S.R., Hauser, R., Schwartz, J., Williams P.L., Smith, T.J., and Christiani, D.C. Association of

Heart Rate Variability with Occupational and Environmental Exposure to Particulate Air Pollution.

Circulation, Vol. 104, pp. 986-991, 2001.

Magari, S.R., Schwartz, J., Williams, P.L., Hauser, R., Smith, T.J., and Christiani, D.C. The Association of

Particulate Air Metal Concentrations with Heart Rate Variability. Environ. Health Perspect. Vol. 110, No.

9, pp. 875-880, September 2002.

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Diesel Exhaust-Like Particles Lodge in the Lung

Autopsies of lungs from non-smoking female residents of Mexico City reveal that fine

particle air pollutants overwhelm the lungs’ clearance mechanisms and are retained in

lung tissue.

The study compared residents of highly polluted Mexico City with residents of the far

cleaner Vancouver, British Columbia, and found significantly higher numbers of particles

imbedded in the lungs of in long-term residents of Mexico City. Some of the particles

retained in the lungs of Mexico City residents resembled diesel exhaust samples. The

study design excluded smokers and those with occupational exposures.

This study provides the first direct evidence that increased lifetime exposure to air

pollution results in higher particle retention in the lung. The findings provide biological

plausibility to epidemiologic studies showing adverse effects of particles from chronic

exposures.

“Our observations indicate that long-term residence in an area of high ambient particle

concentrations is associated with greater numbers of retained particles in the lung; this

shows for the first time that the aggregated ultrafine particles in ambient air can also be

found in lung tissue,” the study concludes.

Brauer, M., Avila-Casado, C., Fortoul, T.I., Vedal, S., Stevens, B., and Chung, A. Air Pollution and

Retained Particles in the Lung, Environ. Health Perspec. Vol. 109, pp. 1039-1043, 2001.

Blood Pressure Rises During Air Pollution Episode

Blood pressure is a well-established risk factor for cardiovascular disease and deaths.

This study used data from a January 1985 air pollution episode in Central Europe, and a

World Health Organization project to monitor measures related to cardiovascular disease

in over 2,000 adults in Augsburg, Germany.

During the air pollution episode, 24-hour concentrations of total suspended particulates

and SO2 were associated with an increase in blood pressure, after adjusting for other risk

factors and weather.

“The observed increase in systolic blood pressure associated with ambient air pollution

could be related to a change in cardiovascular autonomic control,” report the

researchers.

Ibald-Mulli, A., Stieber, J., Wichmann, H.-E., Koenig, W., and Peters, A., Effects of Air Pollution on

Blood Pressure: A Population-Based Approach. Am. J. Public Health, Vol. 91, pp. 571-577, 2001.

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Particle Exposure Causes Lung Inflammation in Laboratory Animals

Researchers used a concentrating device to test whether short-term exposures to ambient

air particles from Boston, MA caused pulmonary inflammation in normal rats and in rats

with chronic bronchitis. Inflammation was assessed by washing the lungs and measuring

concentrations of white blood cells, a marker for inflammation. Concentrated particles

were associated with an increase in inflammation in both the normal and the bronchitic

animals.

The concentrations used in this study were comparable to cumulative 24-hour

concentrations of PM2.5 found in developing countries.

The researchers conclude, “this work demonstrated that short-term exposures to PM2.5

concentrated from Boston’s atmosphere induce an inflammatory reaction in the lungs of

rats. . . .The magnitude of pulmonary inflammation was associated with elements

originating from combustion sources.”

Saldiva, P.H.N., Clarke, R.W., Coull, B.A., Stearns, R.C., Lawrence, J., Murthy, G.G.K, Diaz, E.,

Koutrakis, P., Suh, H., Tsuda, A., and Godleski, J.J. Lung Inflammation Induced by Concentrated Ambient

Air Particles is Related to Particle Composition. Am. J. Respir. Crit. Care Med. Vol. 165, pp. 1610-1617,

2002.

Toxicology Study in Human Volunteers Helps Explain Utah Valley Epidemiology

Studies

The temporary closure of a steel mill in the Utah Valley during a labor dispute in the late

1980’s provided a unique opportunity to study the health of residents during period the

mill was closed, compared to before and after the closure. A series of epidemiological

studies published in the 1990s reported associations between elevated PM concentrations

and increased elementary school absences, bronchitis and asthma hospital admissions for

pre-school aged children, total respiratory hospital admissions, pulmonary function

abnormalities, and mortality.

In what commentators call “a strikingly innovative study”, researchers obtained the

archived air pollution filters from the late 1980s, extracted the particles, and instilled

them in the lungs of healthy human volunteers. The following day, they washed the

lungs to check for signs of inflammation. They found more inflammation in those

exposed to particles from the monitoring site nearest to the steel mill during the years

when the steel mill was operating, compared to when it was closed.

“This is the first demonstration that pulmonary effects after experimental exposure of

humans to PM can correlate with health outcomes observed in epidemiologic studies of

the same material under normal exposure conditions,” the study concluded. Researchers

suggest that the metals contained on the particles may contribute to the toxic effect.

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Ghio, A.J. and Devlin, R.B. Inflammatory Lung Injury after Bronchial Instillation of Air Pollution

Particles. Am. J. Crit. Care Med. Vol. 164, pp. 704-708, 2001.

Beckett, W.S. The Air Pollution Detectives. Am. J. Respir. Crit. Care Med., Vol. 164, No. 4, pp. 515-516,

August 2001.

AIR POLLUTION AND BRAIN DAMAGE

Air Pollution May Play a Role in Alzheimer’s Disease

The nasal cavity is a common route of entry for inhaled air pollutants. A study has

shown that the nasal mucus membrane defenses are severely compromised in children in

Mexico City, diminishing protection from inhaled pollutants. Researchers hypothesized

that inflammatory processes in the respiratory tract could trigger a chain of events

involving the brain.

This study found that Mexico City dogs chronically exposed to high concentrations of

ozone, PM, and other air pollutants had extensive brain damage compared to dogs from a

less polluted city. Researchers observed alterations of the blood-brain barrier,

degenerating, shrunken nerve cells surrounded by dying white matter cells, plaques, and

neurofibrillary tangles.

Researchers concluded that “the histopathology we observed in these urban dogs is of

sufficient magnitude to warrant concern that similar histopathology may be occurring in

humans residing in large polluted metropolitan areas,” and that “persistent pulmonary

inflammation and deteriorating olfactory and respiratory barriers may play a role in the

neuropathology observed in the brains of these highly exposed canines.

Neurodegeneratiave disorders such as Alzheimer’s may begin early in life with air

pollutants playing a crucial role.”

Caldern-Garcidueas, L., Valencia-Salazar, G., Rodrguez-Alcaraz, A., Gambling, T.M., Garca, R.,

Osnaya, N., Villarreal-Caldern, A., Devlin, R.B., and Carson, J.L. Ultrastructural Nasal Pathology in

Children Chronically and Sequentially Exposed to Air Pollutants. Am. J. Respir. Cell Mol. Biol. Vol. 24,

pp. 132-138, 2001.

Caldern-Garcidueas, L., Azzarelli, B., Acuna, H., Garcia, R., Gambling, T.M., Oznaya, N., Monroy, S.,

Del Rosario Tizapantzi, M., Carson, J.L., Villarreal-Calderon, A., and Rewcastle, B. Air Pollution and

Brain Damage. Toxicologic Pathology, Vol. 30, No. 3, pp. 373-389, 2002.

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