hsci 483: children's health and the environment air pollution and children’s health may 12,...
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HSCI 483: Children's Health and the Environment
Air Pollution and Children’s Health
May 12, 2015
Ryan AllenAssociate Professor
SFU Faculty of Health Sciences
Presentation Structure
• Two parts• Basic concepts, background, why is this
important?• (Epidemiologic) evidence of air pollution’s
effects on childhood health and development
LET’S START WITH SOME BASIC CONCEPTS AND BACKGROUND…
4
Particulate Matter (PM)
= PM2.5
5
Population Attributable Fraction(aka Population Attributable Risk)
“…the proportional reduction in population disease or mortality that would occur if exposure to a risk factor were reduced to an alternative ideal exposure scenario (eg. no tobacco use).”
A function of the risk (e.g., RR, OR) and the fraction of the population that is exposed.
http://www.who.int/healthinfo/global_burden_disease/metrics_paf/en/
6
Population Attributable Fraction(aka Population Attributable Risk)
Gordis, Epidemiology, 1996
7
Individuals vs. Populations
“Interpretation In view of both the magnitude of the risk and the prevalence in the population, air pollution is an important trigger of mycardial infarction, it is of similar magnitude (PAF 5-7%) as other well accepted triggers such as physical exertion, alcohol, and coffee. Our work shows that ever-present small risks might have considerable public health relevance.”
8
“…a large number of people at a small risk may give rise to more cases of disease than the small number who are at a high risk.”
Or, in other words…
-Rose, Int. J. Epidemiol. 1985
“A large number of people at a small risk…”
Van Donkelaar, EHP, 2015
“…global population-weighted mean PM2.5 concentrations increased 0.55 ug/m3
/year [2.1%/year] from 1998 through 2012.
5.3 billion people
10
• Proportion of world’s population relying on solid fuels declined from 53% in 1990 to 41% in 2010
• Absolute number of people relying on solid fuels has remained constant at ~2.8 billion people
Smith et al., Annu. Rev. Public Health 2014
“A large number of people at a small risk…”
11
Recently Established “Facts”Location, location, location…
Karner et al., 2010, Environ Sci Tech
Wang et al., 2013, Atmos. Environ
12
Location, Location, Location…
Brauer et al., “Traffic-Related Air Pollution and Health: A Canadian Perspsective on Scientific Evidence and Potential Exposure Mitigation Strategies”, 2012
1/3 of the Canadian population lives within 500 m of a highway or 100 m of a major road.
Nethery et al., 2009
CHAPS = Canadian Human Activity Patterns Survey (subset of women in Vancouver, aged 17-45).
Hours/day in microenvironments (weekdays only)
Model of time spent at/near home during pregnancy
Location, Location, Location…
“…our results indicate that pregnant women tend to spend more time at home during the latter stages of pregnancy…”
Cohen-Hubal et al., 2000
Location, Location, Location…
School: An Important Microenvironment
The ProvinceJanuary 5, 2012
School: An Important Microenvironment
Amram et al., 2011
School: An Important Microenvironment
48-hr personal exposure samples
54 kids at 4 schools
School: An Important Microenvironment
• California legislation (Senate Bill 352, Chapter 668, Statutes of 2003)
“The school district… identify both permitted and nonpermitted facilities…including, but not limited to, freeways and other busy traffic corridors, large agricultural operations, and railyards, within one-fourth of a mile [400 meters] of the proposed school site, that might reasonably be anticipated to emit hazardous air emissions...”
School: An Important Microenvironment
20
“It is the opinion of the writing group that the overall evidence is
consistent with a causal relationship between PM2.5
exposure and cardiovascular morbidity and mortality.”
Recently Established “Facts”
AIR POLLUTION HAS EFFECTS BEYOND
THE LUNG!
Air pollution is now considered the most important environmental carcinogen (more important than second-hand smoke).
“The IARC Working Group unanimously classified outdoor air pollution and particulate matter from outdoor air pollution as carcinogenic to humans (IARC Group 1), based on sufficient evidence of carcinogenicity in humans and experimental animals and strong mechanistic evidence.”
Lancet Oncology, December 2013
Recently Established “Facts”
But what about kids?
• CVD, cancer are diseases of “old age”• So, what about effects in children?
Infant Mortality
Bell & Davis. EHP Supp 2001; 109:389-94; Schwartz, 1994
Infant Mortality
“In a country where infant mortality rates and air pollution levels are relatively low, ambient air pollution as measured by particulate matter contributes to a substantial fraction of infant death, especially for those due to sudden infant death syndrome and respiratory disease.“
Air Pollution and Health• Wide range of outcomes that can be evaluated in
research studies• More severe outcomes generally occur less frequently;
less severe outcomes generally occur more frequently• Significance, interpretation, policy implications
Mortality
Hospital admissions
Emergency visits
Functional limitation
Symptoms Clinical indicators
No adverse health effect
But what about kids?
• CVD, cancer are diseases of “old age”• So, what about effects in children?
– What if chronic exposure to air pollution also affected children’s growth and development?• Fetal growth?• Respiratory infections?• Neurological/cognitive development?• Lung growth?• Allergies?• Asthma development? (as opposed to asthma irritation)
Importance of Early Life Exposure
AGE
DE
VE
LOP
ME
NT
Examples: lung function, cognition
Importance of Early Life Exposure
AGE
DE
VE
LOP
ME
NT
Earlier / more rapid decline
Area is grey is the “cumulative impact” on
health, quality of life, etc.
Importance of Early Life Exposure
AGE
DE
VE
LOP
ME
NT
Failure to reach full “potential”
Importance of Early Life Exposure
AGE
DE
VE
LOP
ME
NT
Relatively subtle changes in developmental “trajectory” early in life…
…may lead to substantial impairments…
…and a major “cumulative” impact over
the life course.
31
Importance of Early Life Exposure
“The developing human brain is inherently much more susceptible to injury caused by toxic agents than is the brain of an adult…
[Developmental] processes have to take place within a tightly controlled time frame, in which each developmental stage has to be reached on schedule and in the correct sequence…If a developmental process in the brain is halted or inhibited, there is little potential for later repair, and the consequences can therefore be permanent.”
32
Importance of Early Life Exposure
Kitaoka et al., 1996. Anat.Rec. 244 :207-213.Thurlbeck et al., 1975. Pathobiol. Annu. 5:1-34.
• Airways and lung development– Full number of generations of conducting
airways developed by 17 weeks gestation– Length and diameter of airways continue to
grow until 5 years of age– Approximately 150 million alveoli present at
birth– Alveoli fully developed (~300 million) by 2-3
years of age.
33
Importance of Early Life Exposure
Sears et al., NEJM, 2003
“These findings, together with persistently low lung function, suggest that outcomes in adult asthma may be determined primarily in early childhood.”
Importance of Early Life Exposure
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
5.00
Household Air Pollution Ambient Air Pollution
Attri
buta
ble
DA
LYs (
%)
4.3%
3.1 %
DALYs= Years of Life Lost (YLL) +
Years Lost Due to Disability (YLD)
0.00
500,000.00
1,000,000.00
1,500,000.00
2,000,000.00
2,500,000.00
3,000,000.00
3,500,000.00
4,000,000.00
Household Air Pollution Ambient Air Pollution
Attri
buta
ble
Dea
ths
CancersChronic Respiratory DiseasesCirculatory DiseasesInfections
3.48 M3.22 M
DEATHS
Data from GBD, http://vizhub.healthdata.org/gbd-compare/
Is it Prenatal Exposure? Postnatal Exposure? Both?
AGE
AIR
PO
LLU
TIO
N E
XP
OS
UR
E
PRENATAL EXPOSUREC
HIL
DH
OO
D E
XP
OS
UR
E
Is it Prenatal Exposure? Postnatal Exposure? Both?
AGE
AIR
PO
LLU
TIO
N E
XP
OS
UR
E
“Because of relatively high correlation between in utero and first-year exposures for many pollutants, we are unable to discern the relative importance of these exposure periods.”
Ginsberg et al., 2005
Extrathoracic Tracheobronchial Bronchioloes Pulmonary
Deposition/surface area of fine particles 2-4 x adults.
Children Are Not Small Adults
• Advantages to studying children– Fewer potentially confounding exposures
(occupational exposure, smoking)– Shorter duration for retrospective exposure
assessment
• Challenges in studying children– Some diagnoses unreliable in young children
(e.g. asthma)– Limitations in health testing (e.g. cognitive
testing in very young children)– Questionnaires rely on caretaker
Heinrich and Slama, 2007
Children Are Not Small Adults
Exposure “Contrasts”
Bell & Davis. EHP Supp 2001; 109:389-94; Schwartz, 1994
• Risk estimates (relative risk, odds ratio) are expressed relative to some exposure contrast or gradient
• Relative risk =
• For example, risk among those living within 100 m of a major road (exposed) vs. risk among those living > 100 m from a major road (unexposed)
Risk in Exposed
Risk in Unexposed
Exposure “Contrasts”
Bell & Davis. EHP Supp 2001; 109:389-94; Schwartz, 1994
• But what if exposure is not binary? What if there is no “unexposed” group?
• In these cases, risk is expressed per exposure contrast, e.g.,– Per 10 µg/m3
contrast in PM2.5
– How does risk at 10 ug/m3
compare to 20 ug/m3?
EXPOSURE
RIS
K
0 10 20
Cities with better air quality
Cities with poorer air quality
Dockery et al., NEJM, 1996
Adjusted for smoking, age, gender, BMI, education, occupational exposure
Cause of DeathMost vs. Least Polluted City
All1.26
(1.08-1.47)
Lung Cancer1.37
(0.81-2.31)
Cardiopulmonary1.37
(1.11-1.68)
All Other1.01
(0.79-1.30)
Exposure “Contrasts”
42
Exposure “Contrasts”
0 10 20 30 40 50 60 70
VancouverHelsinki
San FranciscoMontreal
ChicagoLondon
Los AngelesMexico City
IstanbulMumbai
BeijingUlaanbaatar
Annual Average PM2.5 Concentration (ug/m3)
Example: “…for each 10-μg/m3 increase in PM2.5 exposure, birth weights declined by…48.4 grams.”
A 10 µg/m3 exposure
contrast is approximately the difference between typical concentrations in:
Mexico City vs. London
LA vs. San Francisco
Chicago vs. Vancouver
EFFECTS OF AIR POLLUTION ON CHILDREN’S DEVELOPMENT:
Fetal Growth & Development
Fetal Growth & Development• Indicators
– Birth weight (grams), Low birth weight (<2,500 grams), Small for gestational age (<10th %ile for gestational age), Pre-term birth (<37 weeks gestation)
• Disorders related to fetal growth and length of gestation are the leading cause of death in the first year of life in Canada
• Some evidence linking impaired fetal growth with metabolic syndrome, hypertension, diabetes mellitus, cardiovascular disease, and stroke in adulthood.– DOHaD
• Genetic factors account for 25-50% of the variation in birth weight, birth length, and head circumference.
45
A Growing Research Area
Stieb et al., 2012
Growing Evidence of Solid Fuel Smoke’s
Effects of Fetal Growth
• Systematic review and meta-analysis • OR for LBW = 1.38 (1.25 – 1.52)• OR for stillbirth = 1.51 (1.23 – 1.85)• Mean reduction in birth weight = 96 g (69 – 124 g)**• “Because a majority of pregnant women in developing countries,
where rates of LBW and stillbirth are high, are heavily exposed to indoor air pollution, increased relative risk translates into substantial population attributable risks of 21% (LBW) and 26% (stillbirth)”
**Average effect of smoking during pregnancy on birth weight is a reduction of about 150-200 grams (Andres and Day. Seminars in Neonatology, 2000;5:231-41).
Intervention Studyof Reproductive Outcomes
69 pregnant women randomized to receive a chimney stove vs. 105 controls using open fires
Children of women using stoves had birth weight 89 g (95% CI: -27 – 204) greater than children of women using open fires
48
Pregnant women enrolled into the study
Random Selection
Average birth weight among babies in this
group
Average birth weight among babies in this
group
No Air Filter
UGAAR Study
49
UGAAR Study
http://www.eurasianet.org/node/66662
Adapted from Kannan et al., 2006
Air Pollution
Preterm Birth
Low Birth Weight
Intrauterine Growth
Restriction
Oxidative Stress
InflammationBlood
CoagulationEndothelial
FunctionHemodynamic
Responses
Transplacental Oxygen and Nutrient Transport
Possible Mechanisms
EFFECTS OF AIR POLLUTION ON CHILDREN’S DEVELOPMENT:
Neuropsychological Development
52
Neuropsychological Development
Forns et al., 2012
53
Prenatal Exposure and IQ
Perera et al., Pediatrics, 2009
54
Attention “We examined
associations between black carbon and attention measures ascertained at 7-14 years of age among 174 children in a birth cohort based in Boston.”
“…we found associations between black carbon exposure and higher commission errors and slower reaction time. These associations were overall more apparent in boys than girls.”
Chiu et al., EHP, 2013
55
Autism Risk factors for
autism are poorly understood A few recent studies
have linked early-life exposure to traffic-related air pollution with autism
Volk et al., JAMA Psychiatry, 2013
Case control study in California “Exposure to traffic-
related air pollution…during pregnancy and during the first year of life was associated with autism.”
56
Confounding? Exposure determined, in part, by where
people live.
Several risk factors for neurodevelopmental impairments may also influence where individuals spend their time (i.e., self-selection):
“…maternal mental health status may be a potential confounder…because the increased risk of various adverse neurobehavioral outcomes in offspring…are associated with mothers’ mental health status, which may affect residential choice and thus determine the estimated residential exposures to ambient air pollution during pregnancy or early childhood.”
Block et al., Neurotoxicology, 2012
Possible Mechanisms Direct translocation of particles to the brain
and transfer across the blood brain barrier. BBB not fully developed until ~6 months of age. Post-mortem studies have found PM in the human
brain.
Circulating pro-inflammatory mediators. Activation of microglia, the brain’s resident innate
immune cells and regulators of neuroinflammation.
Key to normal brain function, but chronic activation can lead to neuron and cerebrovascular damage.
Block ML, Elder A, Auten RL, et al. The outdoor air pollution and brain health workshop. Neurotoxicology. Oct 2012;33(5):972-984. Block ML, Calderon-Garciduenas L. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci. Sep 2009;32(9):506-516.
EFFECTS OF AIR POLLUTION ON CHILDREN’S DEVELOPMENT:
Respiratory Infections
Acute Lower Respiratory Infections
• Most important global cause of death in children under 5 (ALRIs 4 million deaths annually)
Smith, 2000; WHO, Fuel for Life, 2006
• Consistent evidence of associations between ALRI and solid fuel use (considered by WHO to be causally linked)
59
60
“In a population heavily exposed to wood smoke from cooking, a reduction in exposure achieved with chimney stoves did not significantly reduce physician-diagnosed pneumonia for children younger than 18 months. The significant reduction of a third in severe pneumonia, however, if confirmed, could have important implications for reduction of child mortality.”
Chronic lung diseases
Cancer
61
Respiratory Infections Cardiovascular
62
Ambient PM and ALRI?
Mehta et al., Air Quality Atmosphere & Health, 2013
EFFECTS OF AIR POLLUTION ON CHILDREN’S DEVELOPMENT:
Lung Growth
• Prospective cohort study• 1,759 children from 12 communities• Measured lung function annually for 8 years
64
Chronic Exposure and Lung DevelopmentThe California Children’s Health Study
• Impaired lung development associated with air pollution (strongest associations for traffic pollutants)
• Pollution-associated deficits were clinically significant by age 18
Gauderman et al, 2004
Chronic Exposure and Lung DevelopmentThe California Children’s Health Study
65
Air Pollution and Lung Function Growth
• 110 children who moved away from communities in the Children’s Health Study
• “We conclude that changes in air pollution exposure during adolescent growth years have a measurable and potentially important effect on lung function growth and performance.”
67
Early-Life Exposure
Morales et al., Thorax, 2015
• Lung function among 620 preschool children (4.5 years)
• Exposure modeled at residence location during pregnancy.
• “Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age.”
EFFECTS OF AIR POLLUTION ON CHILDREN’S DEVELOPMENT:
Asthma
69
An Epidemic
Eder, NEJM, 2006
70
Asthma Trends
Life and Breath, Respiratory Disease in Canada, 2007
Does air pollution cause asthma?
PROBABLY.
Does air pollution cause asthma?NO2 PM2.5
Anderson et al., Air Quality Atmosphere and Health, 2013
“These results are consistent with an effect of outdoor air pollution on asthma incidence.”
73
An Important Role for Traffic Emissions
“How often do trucks pass through the street where you live, on weekdays?”
Does air pollution cause asthma?
“Based on this evidence, the UK’s Committee on the Medical Effects of Air Pollutants recently concluded that, overall, the evidence is consistent with the possibility that outdoor air pollution might play a role in causing asthma in susceptible individuals living very close to busy roads carrying a lot of truck traffic.”
Does air pollution cause asthma?
Gene x Environment
MacIntyre et al., EHP, 2014
“GSTP1 (the glutathione S-transferase pi gene) codes for an enzyme that metabolizes reactive oxygen species in the lung.”
Summary of Vancouver ResultsAir Pollution Effects on Children in a City with “Low” Levels of Air Pollution
MacIntyre et al., Epidemiology, 2011
• Arguably the best air quality of any major city in the world• Some evidence of associations for all of these effects• Evidence not entirely consistent across all pollutants or exposure
assessment methods• Traffic-related air pollution most consistently associated
Final Messages
1) The health impacts of air pollution are preventable.
2) The most effective way to reduce exposure to air pollution is to produce less air pollution.
3) Less pollution = Better health
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