air pollution and health

84
AIR POLLUTION AND AIR POLLUTION AND HEALTH HEALTH MEDICAL EVIDENCE MEDICAL EVIDENCE SUMMARY SUMMARY Clay Ballantine, M.D. Clay Ballantine, M.D.

Upload: chad

Post on 22-Jan-2016

19 views

Category:

Documents


0 download

DESCRIPTION

AIR POLLUTION AND HEALTH. MEDICAL EVIDENCE SUMMARY Clay Ballantine, M.D. Medical Studies. Peer-reviewed journals Thousands of studies Physiology Epidemiology Government databases Dose-Response relationship. Causes of Death in U.S. 1. Cardiovascular Disease 2. Cancer - PowerPoint PPT Presentation

TRANSCRIPT

Page 1: AIR POLLUTION AND HEALTH

AIR POLLUTION AND AIR POLLUTION AND HEALTHHEALTH

MEDICAL EVIDENCEMEDICAL EVIDENCE

SUMMARYSUMMARY

Clay Ballantine, M.D.Clay Ballantine, M.D.

Page 2: AIR POLLUTION AND HEALTH

Medical StudiesMedical Studies

Peer-reviewed journals

Thousands of studies

Physiology

Epidemiology

Government databases

Dose-Response relationship

Page 3: AIR POLLUTION AND HEALTH

Causes of Death in U.S.Causes of Death in U.S.

1. Cardiovascular Disease

2. Cancer

3. Lung Disease

Page 4: AIR POLLUTION AND HEALTH

Annual DeathsAnnual Deaths

Air Pollution 23,000

Drunk Driving 17,000

Murder 20,000

Page 5: AIR POLLUTION AND HEALTH

NC Medical Society ResolutionNC Medical Society Resolution

2001 House of Delegates unanimously adopted a resolution sponsored by the Buncombe Co. Medical Society, urging all branches of state government to work toward cleaner air because of the large public health impact of air pollution exposure.

Page 6: AIR POLLUTION AND HEALTH

RISKRISK

Assumed vs. Imposed

Page 7: AIR POLLUTION AND HEALTH

Who is at Risk?Who is at Risk?

Children Elderly Prior heart or lung disease patients Diabetics Persons who work/exercise outdoors Otherwise healthy adults and children

Page 8: AIR POLLUTION AND HEALTH

Health ProblemsHealth Problems Impaired fertility Birth Defects / Still births Respiratory Infections Asthma Emphysema Lung Cancer Heart attacks Strokes Premature Death

Page 9: AIR POLLUTION AND HEALTH

““Pyramid of Effects” Pyramid of Effects”

lung function changes, immune cell responses, heart rate or heart rate variability responses

Asthma attacks, medication use, symptoms

Doctor visits

Hospital Admissions

Death

Page 10: AIR POLLUTION AND HEALTH

4 Main Pollutants4 Main Pollutants

Ozone, ground-levelParticulates, especially PM 2.5Air-borne toxicsMercury

Page 11: AIR POLLUTION AND HEALTH

Air Pollutants:Air Pollutants: Ground Level Ozone Ground Level Ozone

Ultra-violet light

Volatile organics

Nitrogen oxides

Page 12: AIR POLLUTION AND HEALTH
Page 13: AIR POLLUTION AND HEALTH

Ozone’s physiologyOzone’s physiology

Caustic Gas

Acute and Chronic lung damage

Page 14: AIR POLLUTION AND HEALTH

Airway ObstructionAirway ObstructionAirway ObstructionAirway Obstruction

Page 15: AIR POLLUTION AND HEALTH

Ozone and Asthma AttacksOzone and Asthma Attacks

Hundreds of published studies from around the world all show the same results:

More ozone pollution exposure leads to more asthma attacks.

Dose = Response relationship

Page 16: AIR POLLUTION AND HEALTH

Asthma EpidemicAsthma Epidemic

50 % in Children

100% in Adults

Page 17: AIR POLLUTION AND HEALTH

North Carolina SummersNorth Carolina Summers

Air pollution causes an EXTRA:

240,000 Asthma Attacks 6,300 ER Visits 1,900 Admissions

(Abt Associates, 1999)

Page 18: AIR POLLUTION AND HEALTH

Asthma and Air PollutionAsthma and Air Pollution

Epidemiologic analysis of air quality data from 1997 and asthma rates showed:

One third to one half of asthma attacks in North Carolina annually are due to air pollution exposure

Abt Associates report, 1999

Page 19: AIR POLLUTION AND HEALTH

Ozone: Asthma EffectsOzone: Asthma EffectsMore people with asthmaMore asthma attacksMore asthma medicine useMore doctor, ER and Urgent Care visitsMore children and elderly in hospitalsMore school absencesMore lost work days

Page 20: AIR POLLUTION AND HEALTH

Ozone: Other EffectsOzone: Other Effects

allergy symptoms

respiratory infections

ear infections

emphysema attacks

overall death rates

Page 21: AIR POLLUTION AND HEALTH

Ozone Pollution Health RisksOzone Pollution Health RisksThe ALA “Worst 25”-2004The ALA “Worst 25”-2004

Knoxville 9th

New York 13th

Charlotte 14th

Greensboro-Winston 16th

Atlanta 21st

Raleigh-Durham 23rd

Page 22: AIR POLLUTION AND HEALTH
Page 23: AIR POLLUTION AND HEALTH

By 2010 vehicle use will grow 70% and electricity use 50%.By 2010 vehicle use will grow 70% and electricity use 50%.

By 2040 vehicle use will grow 170% and electricity 100%.By 2040 vehicle use will grow 170% and electricity 100%.

Page 24: AIR POLLUTION AND HEALTH

Air Pollutants: ParticulatesAir Pollutants: Particulates

Sulfates, nitrates,

Polycyclic Aromatic Hydrocarbons (PAH),

Soot / Carbon

and Dust

Page 25: AIR POLLUTION AND HEALTH

Air Pollutants: ParticulatesAir Pollutants: Particulates

Variable sources:

30-70% from traffic

70-30% from power plants and industry

Page 26: AIR POLLUTION AND HEALTH

Air Pollutants: ParticulatesAir Pollutants: Particulates

Year round exposures

Penetrate buildings

Page 27: AIR POLLUTION AND HEALTH

Particulate PollutionParticulate Pollution

Page 28: AIR POLLUTION AND HEALTH

Particulate PhysiologyParticulate Physiology

Penetrate deeply into lungs

Irritate lungs and airways

Systemic inflammation

Page 29: AIR POLLUTION AND HEALTH

Two Different Immune Two Different Immune System ResponsesSystem Responses

Th1 = Normal infection fighting response

Th2 = Allergic/Asthmatic response

Page 30: AIR POLLUTION AND HEALTH

Diesel Exhaust Permanently Diesel Exhaust Permanently Changes Immune ResponseChanges Immune Response

More Asthmatic and Allergic responsesIncreases Th2 Decreases Th1Polycyclic aromatic hydrocarbons

(PAH) are the culpritsDiesel and vehicle exhaust and coal

smoke

Nel, A.E., et al., J of Allergy and Clinical Immunology, 2001

Page 31: AIR POLLUTION AND HEALTH

Particulates and AsthmaParticulates and Asthma

• Multiple studies show direct correlation between exposure to particulates and increases in asthma attacks and hospitalization rates

• Effects seen in adults and especially pronounced in children

Page 32: AIR POLLUTION AND HEALTH
Page 33: AIR POLLUTION AND HEALTH

Particulates: Cardiac EffectsParticulates: Cardiac Effects

Vascular inflammation

Blood clotting protein levels

Cardiac arrhythmias

Blood pressure

Heart rate variability

Alters cardiac conduction

Page 34: AIR POLLUTION AND HEALTH

Particulates: Cardiac EffectsParticulates: Cardiac Effects

Vascular inflammation is more important than cholesterol in development of cardio-vascular disease

Page 35: AIR POLLUTION AND HEALTH

Air Pollution and Air Pollution and Next-Day Heart AttacksNext-Day Heart Attacks

Short term exposure to particulates (PM2.5) increases the incidence of heart attacks for one day following exposure

As air pollution goes up the risk of heart attack goes up

Increased Particulate Air Pollution and the Triggering of Myocardial Infarction Peters, et al.; Circulation, June 12, 2001, vol. 103

Page 36: AIR POLLUTION AND HEALTH
Page 37: AIR POLLUTION AND HEALTH

Traffic Emissions Traffic Emissions and Deathand Death

Compared two groups:

People living near a main road and those farther from traffic-related particulates and diesel exhaust.

Hoek, G., et al. “Association between Mortality and Indicators of Traffic-related Air Pollution in the Netherlands: A Cohort Study” Lancet 360 (2002) 1203

Page 38: AIR POLLUTION AND HEALTH

Traffic Emissions Traffic Emissions and Deathand Death

Near-road group had:

Almost double the death rate from heart and lung disease

1.4 times higher overall death rate

Hoek, G., et al. “Association between Mortality and Indicators of Traffic-related Air Pollution in the Netherlands: A Cohort Study”

Lancet 360 (2002) 1203

Page 39: AIR POLLUTION AND HEALTH

Tunnel WorkersTunnel WorkersParticulate Exposure StudyParticulate Exposure Study

Swedish automobile tunnel workers

Higher incidences of cardiac events (heart attacks and deaths)

due to exposure to particulates at tunnel work stations

Bellander, T.,Dept. of Environmental Health, Sweden, WHO/HEI Conference March, 2001

Page 40: AIR POLLUTION AND HEALTH

Lung Cancer, Cardiopulmonary Lung Cancer, Cardiopulmonary Mortality, and Long-term Exposure Mortality, and Long-term Exposure

to Fine Particulate Air Pollutionto Fine Particulate Air Pollution

Air pollution increases the incidence and death rates from lung cancer

Dose-Response relationship

Pope, et al. JAMA 2002 ;287:1132-1141

Page 41: AIR POLLUTION AND HEALTH

Lung Cancer… (Pope, et al)Lung Cancer… (Pope, et al)

Risk increase:

Same as living with a smoker

(second-hand smoke exposure)

Pope, et al. JAMA 2002 ;287:1132-1141

Page 42: AIR POLLUTION AND HEALTH

Air Pollution and Air Pollution and Stroke Deaths Stroke Deaths

Fine particulate matter and gaseous pollutants are significant risk factors for acute stroke death

More air pollution exposure=more acute stroke deaths

Effect of Air Pollutants on Acute Stroke Mortality. Hong, et al.

Feb., 2002; Environmental Health Perspectives, v. 110. no.2

Page 43: AIR POLLUTION AND HEALTH

Long-term Effects of Particulate Long-term Effects of Particulate Pollution ExposurePollution Exposure

Up to 4% of all US deaths

1 to 3 year drop in life expectancy

(smokers lose ~4-15 years)

5% of all cardiac hospitalizations

Effects on healthy people as well

Page 44: AIR POLLUTION AND HEALTH

Lack of Threshold Effect: Lack of Threshold Effect: Nowhere to hideNowhere to hide

Daniels et al “NMMAPS” Am J Epidemiology v.152, no. 5. (2000)

Page 45: AIR POLLUTION AND HEALTH

Area Cities at Risk: EPA limitsArea Cities at Risk: EPA limits>15 mcg/m>15 mcg/m33 PM 2.5 Weighted PM 2.5 Weighted

Annual MeanAnnual Mean• Charlotte = 17.2• Raleigh = 16.5• Greensboro = 17.8 • Atlanta = 21.4• Greenville, SC = 16.5• Johnson City, TN = 16.4• Asheville = 15.1

EPA data 2000

Page 46: AIR POLLUTION AND HEALTH

Diesel Exhaust Health EffectsDiesel Exhaust Health EffectsNorth Carolina (Annually)North Carolina (Annually)

Deaths 301

Heart Attacks 347

Asthma Attacks6518

Lost Work Days39,589

Diesel and Health in America: The Lingering Threat Diesel and Health in America: The Lingering Threat

Clean Air Task Force and Southern Alliance for Clean EnergyClean Air Task Force and Southern Alliance for Clean Energy

Feb., 2005Feb., 2005

Page 47: AIR POLLUTION AND HEALTH

Annual Deaths Due to Annual Deaths Due to Power Plant ParticulatesPower Plant Particulates

#4 North Carolina 1800#5 Florida 1740#7 Georgia 1630#8 Tennessee 1440#10 Virginia 1240#11 Alabama 1110#14 Kentucky 997#18 South Carolina 791

Page 48: AIR POLLUTION AND HEALTH

Effects on ChildrenEffects on Children--A Generation at Risk----A Generation at Risk--

American Academy of Pediatrics

Policy Statement

Ambient Air Pollution:

Health Hazards to Children

Pediatrics Vol.114 No.6 December, 2004Pediatrics Vol.114 No.6 December, 2004

Page 49: AIR POLLUTION AND HEALTH

Effects on ChildrenEffects on Children--A Generation at Risk----A Generation at Risk--

More vulnerable to adverse effects

80% of lung growth occurs in childhood

Smaller size=higher dose

More time outdoors

Page 50: AIR POLLUTION AND HEALTH

Effects on ChildrenEffects on Children--A Generation at Risk----A Generation at Risk--

Multiple birth defects-heart, neural tubeHigher infant mortalityMore asthmaImpaired lung developmentPremature emphysemaIncreased respiratory infectionsHigher health care expenditures

Page 51: AIR POLLUTION AND HEALTH

Childhood asthmaChildhood asthma

Increased by 55% from 1982-1996

#1 cause of hospitalization (< 18 yrs)

#1 health care cost for childhood diseases

#1 cause lost school days (chronic illness )

1/2 to 1/3 of NC asthma due to air pollution

Page 52: AIR POLLUTION AND HEALTH

Asthma in Buncombe CountyAsthma in Buncombe County

10% Children diagnosed with asthma

25-30% Asthma symptoms

Similar results in all North Carolina counties

NC Dept. HHS-Div. Of Public Health, 2001

Page 53: AIR POLLUTION AND HEALTH

Ozone Causes AsthmaOzone Causes Asthma

Exercising children exposed to ozone: a cohort study

time outdoors = asthma

McConnell, et al. Lancet 2002: 359: 386-91

Page 54: AIR POLLUTION AND HEALTH

Air Pollution and Air Pollution and Lung Function Growth-Part 1Lung Function Growth-Part 1

1700 4th graders followed for 4 years

10% lower lung function for children growing up in more polluted air

Most time in polluted air = worst impairment of lung growth

Association between Air Pollution and Lung Function Growth in Southern California Children. Gauderman, W., et al., Am J Respiratory and Critical Care Medicine, vol.166 (2002) pp.76-84.

Page 55: AIR POLLUTION AND HEALTH

Air Pollution and Air Pollution and Lung Function Growth-Part 2Lung Function Growth-Part 2

1700 4th graders followed for 8 years

20% lower lung function for children growing up in more polluted air

The Effect of Air Pollution on Lung Development from 10 to 18 Years of AgeThe Effect of Air Pollution on Lung Development from 10 to 18 Years of Age

Gauderman, W., et al., Gauderman, W., et al.,

New England Journal of Medicine Vol. 351 (2004) pp 1057-1067New England Journal of Medicine Vol. 351 (2004) pp 1057-1067

Page 56: AIR POLLUTION AND HEALTH
Page 57: AIR POLLUTION AND HEALTH

School Busses and Child HealthSchool Busses and Child Health

Diesel exhaust worsens asthma and allergy symptoms and increases lung cancer risk

Exhaust exposure is 4 times higher inside school bus vs. car and 20-40 times greater than EPA cancer risk thresholds

www.epa.gov/cleanschoolbus

www.nrdc.org/air/transportation/schoolbus/sbusinx.asp

Page 58: AIR POLLUTION AND HEALTH

Air Pollution and Air Pollution and Medical Care CostsMedical Care Costs

Every 10 ppb particulates=

$177 extra cost to Medicare per patient per year

Air Pollution and Medical Care Use by Older Americans: A Cross Area Analysis. Fuchs, Victor and Rosen, Sarah

Health Affairs, vol. 21, no. 26 pp207-214

Page 59: AIR POLLUTION AND HEALTH

Air Pollution and Air Pollution and Medical Care CostsMedical Care Costs

Raleigh=

$35 Million

extra Medicare costs

per year

Page 60: AIR POLLUTION AND HEALTH

Annual Asthma Costs: NCAnnual Asthma Costs: NC

NC 7th & 8th Graders:

$14 million Hospitalizations

$ 1.4 million E.R. visits

All NC children:

$100 million Add M.D. visits, prescription costs, wages lost by parents who miss work, and costs for other children’s age groups

NC Dept. HHS-Div. Of Public Health, 2001

Page 61: AIR POLLUTION AND HEALTH

Asthma Costs:Asthma Costs: Buncombe County Buncombe County

~50% Children in BC are onMedicaid

25-30% Asthma symptoms (10% diagnosed)

$400,000 BCHD budget devoted to asthma care per year

NC Dept. HHS-Div. Of Public Health, 2001

Page 62: AIR POLLUTION AND HEALTH

Cost Shifting-We all payCost Shifting-We all pay

• Health care costs not paid by the auto, trucking, oil and electric concerns that generate pollution

• Private insurance premiums• Lost school revenue for absences• Federal taxes for Medicare (especially for the

elderly)• State taxes for Medicaid (especially for children

and disabled)• County taxes for BCHD • Hospital and health care providers pass on the

costs of the uninsured

Page 63: AIR POLLUTION AND HEALTH

Cost Shifting-We pay MORECost Shifting-We pay MORE

US Government Accounting Office estimates:

Every $1 spent on air pollution control has saved at least $7 in health care costs

Page 64: AIR POLLUTION AND HEALTH

Southeast RegionSoutheast Region

33,000,000 people living in significant air pollution

11,000 excess deaths yearly due to air pollution

$20 billion in excess health care costs per year

Page 65: AIR POLLUTION AND HEALTH

SAMI Data Independent analysisSAMI Data Independent analysis

EPA, NPS, USFS commissioned separate, more comprehensive (but still very limited) health impact assessment of SAMI data,

$11.5 billion to $44 billion annual health care savings in SE U.S. depending on degree of PM 2.5 reduction by 2010

Page 66: AIR POLLUTION AND HEALTH

Impaired Visibility = ParticulatesImpaired Visibility = Particulates

Page 67: AIR POLLUTION AND HEALTH

SAMI Data Independent analysisSAMI Data Independent analysis

$1 billion to $3 billion

annual recreation and tourism benefits lost due to air pollution and haze

Page 68: AIR POLLUTION AND HEALTH

Results of Clean-upResults of Clean-up

1996 Atlanta Summer Olympics, reduced ozone levels due to transit system changes led to a significant drop in children’s asthma.

After German reunification, pollution dropped and children’s respiratory symptoms decreased dramatically.

Friedman, M.S., et al. JAMA, V. 285, No. 7, 2001

Heinrich, J., et al., Am. J. Resp. and Crit. Care Med., V.161, 2000

Page 69: AIR POLLUTION AND HEALTH

Results of Clean-upResults of Clean-up

Ireland banned coal burning: Cardiovascular death rates dropped 10.5%

Hong Kong banned high-sulfur fuel oil: Cardiovascular death rates dropped 2.5%

Page 70: AIR POLLUTION AND HEALTH

Results of Clean-upResults of Clean-up

Utah Valley steel mill closure (Salt Lake City) decreased particulate levels:

Children’s asthma hospitalizations dropped 75%.

Children relocating to less polluted areas: Lung functions improved.

Page 71: AIR POLLUTION AND HEALTH

5 Pieces to the Pollution Puzzle:5 Pieces to the Pollution Puzzle:

1 Our Smokestacks

2 Regional Smokestacks

3 Vehicles

4 Land Use and Transportation Planning—containing sprawl

5 Non-road engines—lawn, farm, marine, rail, construction, recreation and industrial

Page 72: AIR POLLUTION AND HEALTH

Final PointsFinal Points

• Health and economic issue

• Prioritize air quality improvement in decision making

• Over half the problem is traffic

• Massive hidden health costs in transportation and power pollution

• Imposed risk on all population groups, especially our children and elderly

Page 73: AIR POLLUTION AND HEALTH
Page 74: AIR POLLUTION AND HEALTH

5 Pieces to the Pollution Puzzle:5 Pieces to the Pollution Puzzle:

1 Our Smokestacks

NC Clean Smokestacks Act

We are paying to clean up our power plants

Energy efficiency-Energy Star program

Move to wind and solar away from fossil fuels

Page 75: AIR POLLUTION AND HEALTH

5 Pieces to the Pollution Puzzle:5 Pieces to the Pollution Puzzle:

2 Regional Smokestacks

Strengthen and enforce the Clean Air Act

at the federal level

Negotiate with our neighboring states/TVA

Sue Thy Neighbor

Page 76: AIR POLLUTION AND HEALTH

Daily SODaily SO44 Aerosol & its Change on July 15, 1995 for a 10% Aerosol & its Change on July 15, 1995 for a 10%

Reduction of 2010 Strategy A2 SOReduction of 2010 Strategy A2 SO22EmissionsEmissions

+0.15+0.15

+0.05+0.05

- 0.05- 0.05

- 0.15- 0.15

- 0.25- 0.25

- 0.35- 0.35

- 0.45- 0.45

- 0.55- 0.55mmg/mg/m33

(Class 5 day)(Class 5 day)

Page 77: AIR POLLUTION AND HEALTH

Daily SODaily SO44 Aerosol & its Change on July 15, 1995 for Aerosol & its Change on July 15, 1995 for

a 10% Reduction of 2010 Strategy A2 SOa 10% Reduction of 2010 Strategy A2 SO22 Emissions Emissions

+0.15+0.15

+0.05+0.05

- 0.05- 0.05

- 0.15- 0.15

- 0.25- 0.25

- 0.35- 0.35

- 0.45- 0.45

- 0.55- 0.55mmg/mg/m33

(Class 5 day)(Class 5 day)

Page 78: AIR POLLUTION AND HEALTH

5 Pieces to the Pollution Puzzle:5 Pieces to the Pollution Puzzle:

3 Vehicles-the primary urban polluters

Car purchase is the most important environmental decision you will make

Alternative fuel / hybrid carsInclude SUVs, light trucks and minivans in standardsConvert vehicle fleetsLow sulfur fuel—statewide at all grades of gas and

dieselEnforce diesel improvements/decrease truck stop

idlingClean up school busses

Page 79: AIR POLLUTION AND HEALTH

NC Clean Cars Act-2005NC Clean Cars Act-2005

California type standards

House Bill 1460 and Senate Bill 1006

Primary Senate Sponsor: Senator Clodfelter

House Speaker: Rep. Jim Black

In Committee now, public pressure needed

Page 80: AIR POLLUTION AND HEALTH

5 Pieces to the Pollution Puzzle:5 Pieces to the Pollution Puzzle:

4 Land Use and Transportation Planning

More lanes=more sprawl (Atlanta)

Better “Transportation” solutions

Decrease Vehicle miles traveled

Mass Transit funding

Bikeways, sidewalks, greenways an integral part of the transport plan (obesity epidemic)

Page 81: AIR POLLUTION AND HEALTH

5 Pieces to the Pollution Puzzle:5 Pieces to the Pollution Puzzle:

5 Non-road engines—lawn, farm, marine, rail, construction, recreation and industrial

Federal regulation of all forms of diesel and gas engines

Retrofit with catalytic converters

Electric and push mower programs

Page 82: AIR POLLUTION AND HEALTH

Web SitesWeb Sites www.lungusa.org (Annotated Bibliography of

Recent Studies…) www.lungnc.org www.healtheffects.org (Understanding the

Health Effects of Components of the Particulate Matter Mix: Progress and Next Steps)

www.epa.gov/airnow www.nga.org www.landofsky.org/airquality www.cleartheair.org www.airtrust.org www.saminet.org

Page 83: AIR POLLUTION AND HEALTH

Particulate Pollution and All Particulate Pollution and All Cause Mortality (PM10)Cause Mortality (PM10)

For combined heart and lung disease death rates, changes of PM10 particulate pollution of 10 mcg/m3 led to increases in mortality of:

 0.7% Schwartz, et al., 1994 (Six Cities Study)1.0% Dockery and Pope, 1994 (American Cancer

Society Study)1.0% Confirmation reanalysis of the two above

studies by HEI panel, 19960.4% APHEA Project (Air Pollution and Health: A

European Approach) 1997 0.5% Fine Particulate Air Pollution and Mortality in

20 U.S. Cities (NEJM12/14/00, Samet et al.)

Page 84: AIR POLLUTION AND HEALTH

Effects on ChildrenEffects on Children--A Generation at Risk----A Generation at Risk--

Bobak and Leon, Epidemiology 1999; 10:666-670

Loomis, et al., Epidemiology 1999; 10: 118-123

Woodruff, et al., Environ. Health Perspectives 1997; 105: 607-612

Tolbert, et al., Am. J. Epidemiology 2000; 151: 798-810

Gauderman, J.W., et al., Am. J. Respir. And Crit. Care Med. Vol. 162, 2000