Can Timing of Exposure Predispose Older Adults to Disease?

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Can Timing of Exposure Predispose Older Adults to
Disease?

• Douglas W. Dockery
• Effects of Air Pollution on Health of Older
  Adults
• June 14-15, 2005
• Mickey Leland National Urban Air Toxics Research
  Center

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Loss of Function with Age
Brain Weight (92)
Nerve Conduction Velocity (90)
Basal Metabolism (84)
Cardiac Output (70)
Kidney Filtration Rate (69)
Maximum Breathing Capacity (43)
Leap, Scientific American 1973
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And so from hour to hour We ripe and ripe,And
from hour to hourWe rot and rot.

• Shakespeare
• As You like It

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Just as a twig is bent the tree inclines.

• Alexander Pope
• Moral Essays

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Chronic Obstructive Lung Disease

• Cumulative loss of function (FEV1) from
  environmental insults during adulthood
• Maximum attained function determined by growth
  (development) during childhood
• Cumulative effects of environmental insults on
  growth retardation
• Early childhood effects during lung development
• Pre-natal or genetic factors define track (growth
  curve)

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Six Cities Mortality Study

• 8111 adults followed up from 1974 to 1989
• Mortality risk ratios
• Adjustment
• Age, Sex
• Cigarette Smoking
• Occupational Exposure, Education
• Body Mass Index
• Chronic Disease
• Compared to city-specific average PM2.5 (1979-86)

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Six Cities Cohort Mortality
Steubenville
Kingston
St. Louis
Topeka
Watertown
Portage
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Six Cities Mortality Follow-up

• 1974 to 1989 follow-up
• Annual returned postcards and National Death
  Index
• 1,364 deaths in 104,243 person years
• PM2.5 measurements 1979-1986

• 1990 to 1998 follow-up
• National Death Index search
• 1,368 deaths in 54,735 person years
• PM2.5 estimated from PM10 1990-1998

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Six Cities Cohort Follow-up
Steubenville
Kingston
St. Louis
Topeka
Portage
Watertown
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Dublin Coal Ban

• Sept 1, 1990marketing, sale, and distribution of
  bituminous coals banned within city of Dublin.
• Effect was an immediate and permanent reduction
  in average particulate concentrations.
• Average black smoke concentrations declined by
  35.6 mg/m3 (70) after the ban on coal sales.

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Dublin Coal Ban

• Total (non-trauma) death rates decreased by 57
  (plt00001)
• Cardiovascular deaths by 103 (plt00001)
• Respiratory deaths by 155 (plt00001)
• Effects seen within the same season

Clancy et al, Lancet, 2002
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Chronic Obstructive Lung Disease

• Cumulative loss of function (FEV1) from
  environmental insults during adulthood
• Maximum attained function determined by growth
  (development) during childhood
• Cumulative effects of environmental insults on
  growth retardation
• Early childhood effects during lung development
• Pre-natal or genetic factors define track (growth
  curve)
• Death more likely from acute events
• Pneumonia
• Acute cardiac event

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Coronary Heart Disease

• Atherosclerosis
• Plaque builds up in arteries over time
• Can signficantly reduce blood flow
• Carotid intima-media thickness (CIMT)
• Ultrasound measure of atherosclerosis in carotid
  artery
• Correlates well with coronary artery
  atherosclerosis
• Associated with age and sex
• Associated with long-term exposures to smoking
  and passive smoking

? Men ? Women
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IMT by age in patients with heterozygous familial
hypercholesterolaemia (FH) and low-risk controls.
Each dot represents the average IMT of 10 carotid
and femoral IMTs of a subject. Kastelein et
al,Atherosclerosis Suppl 4 2003 31-6
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Ambient Air Pollution and Atherosclerosis in Los
Angeles Kuenzli et al, EHP 2005

• 798 participants in 2 clinical trials
• Carotid intima-media thickness (CIMT) subclinical
  atherosclerosis.
• Geocoded resident to assign annual mean PM2.5.

• 10 mg/m3 increase in mean PM2.5
• associated with 5.9 (p0.018) increase in CIMT
• Stronger associations in Women and Older subjects

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Linkage of Atheroschlerotic Plaques and Acute
Myocardial Infarction
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Determinants of MI Onset StudyPeters et al,
Circulation 2001

• 833 patients with confirmed myocardial infarction
  interviewed in the greater Boston area between
  1995 and 1996.
• Hourly PM2.5 data available during this period
  (24h-average 12.1 µg/m3 max 47.4 µg/m3).

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PM2.5 and Onset of Myocardial Infarction
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Coronary Heart Disease

• Cumulative build-up of plague in coronary
  arteries during adulthood
• CIMT associatd with long term environmental
  exposures (active and passive smoking, air
  pollution)
• Developing evidence that plague buildup begins in
  childhood
• Pre-natal or genetic factors may define track
  (growth curve)
• Death more likely from acute events
• Plaque rupture, myocardial infarction, ischemic
  stroke

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Implantable Cardioverter Defibrillators (ICD)
Devices

• Implanted under skin with electrodes and leads
  attached to heart
• Monitor cardiac rhythm abnormalities
• On detecting potentially fatal arrhythmia,
  triggers cardioverter shock
• Records date and time of all detected arrhythmias
  and therapies

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Air Pollution and Incidence of Cardiac
ArrhythmiasDockery et al, EHP June 2005

• 203 patients with Implanted Cardioverter
  Defibrillators (ICDs)
• Lived within I-495 in eastern Massachusetts
• Followed 1995-2002, average 3.2 years
• Abstracted ICD detected ventricular arrhythmias
• Confirmed by cardiac electrophysiologist

• Daily air pollution measurements
• PM2.5, Black Carbon, SO4
• CO, O3, NO2 and SO2
• Weather
• Temperature and humidity
• Regression of cardiac arrhythmias against air
  pollution

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Air Pollution and Incidence of Cardiac
Arrhythmias Dockery et al, EHP June 2005

• ICD detected ventricular arrhythmias (VA) in 203
  patients in Boston
• Increased risk of VA with 2-day mean PM2.5, Black
  Carbon, CO and NO2 for patients with a recent,
  previous arrhythmia
• Air pollution is acute trigger of potentially
  life-thratening VA among patients with
  electrically unstable cardiac substrate

Prior VA
No Prior VA
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Environmental Effects on the Elderly

• Compromised Substrate
• Cumulative loss of function in adults
• Compromise begins during childhood
• Prenatal (genes) define growth curve (track)
• Acute Trigger
• Environmental exposures can also trigger acute
  response
• With compromised substrate (inadequate reserve),
  pushed over edge

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Timing of Air Pollution Exposures

• Acute exposures (hours to days) can trigger
  adverse events, particularly in the presence of
  compromised substrate
• Medium term exposures (weeks to months) also can
  trigger adverse events
• Long-term exposures (years to decades) can
  contribute to compormised substrate or loss of
  physiologic reserve
• Early life exposures (perinatal and childhood)
  can define track for development of chronic
  condidtions