Transcript Can Timing of Exposure Predispose Older Adults to Disease?

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
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
Death (Harvesting)
And so from hour to hour
We ripe and ripe,
And from hour to hour
We rot and rot.
Shakespeare
As You like It
PreNatal
Genetic
Childhood
Experience
Early
Childhood
Experience
Rapid Decline
Just as a twig is bent
the tree inclines.
Alexander Pope
Moral Essays
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)
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)
Six Cities Cohort Mortality
Mortality Risk Ratio
1.4
1.3
Steubenville
Kingston
1.2
St. Louis
1.1
Topeka
Watertown
1.0
Portage
0.9
0.8
0.7
0
5
10
15
20
PM2.5 (mg/m3)
25
30
35
Six Cities Mortality Follow-up
• 1974 to 1989 follow-up • 1990 to 1998 follow-up
– Annual returned
postcards and National
Death Index
– 1,364 deaths in 104,243
person years
– PM2.5 measurements
1979-1986
– National Death Index
search
– 1,368 deaths in 54,735
person years
– PM2.5 estimated from
PM10 1990-1998
Six Cities Cohort Follow-up
Mortality Risk Ratio
1.4
1.3
Steubenville
Kingston
St. Louis
1.2
1.1
Topeka
Portage
1.0
0.9
0.8
Watertown
0.7
0
5
10
15
20
PM2.5 (mg/m3)
25
30
35
Dublin Coal Ban
• Sept 1, 1990:marketing,
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.
Dublin Coal Ban
• Total (non-trauma) death
rates decreased by 5·7%
(p<0·0001)
• Cardiovascular deaths by
10·3% (p<0·0001)
• Respiratory deaths by
15·5% (p<0·0001)
• Effects seen within the
same season
Clancy et al, Lancet, 2002
Dublin County Borough
40
35
Black
Smoke
600
Deaths
30
400
25
200
20
0
15
1
3
5
7
9 11 13 15 17 19 21 23 25 27 29 31
January 1982
Deaths
Black Smoke (ug/m3)
800
Dublin 1980-1990
17
Deaths per Day
16
15
14
13
12
11
Mean of 20 consecutive points
10
9
0
100
200
300
3 Day Mean Black Smoke (ug/m3)
400
Reversible Decline
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
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
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
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% (p=0.018)
increase in CIMT
•Stronger associations in Women
and Older subjects
Linkage of Atheroschlerotic Plaques and
Acute Myocardial Infarction
Determinants of MI Onset Study
Peters 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).
PM2.5 and Onset of Myocardial Infarction
1.8
24 Hr PM2.5
OR for MI Onset
1.6
1.4
1.2
1.0
0.8
1.6-6.4
6.5-8.6
8.7-11.5
11.6-16.2
PM2.5 (mg/m3)
16.3-52.2
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
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
Air Pollution and Incidence of Cardiac Arrhythmias
Dockery 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
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 lifethratening VA among
patients with electrically
unstable cardiac
substrate
Prior VA
No Prior VA
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
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