relationships between air quality, health and...

Relationships between Air Quality,Health and Economy

C. Arden Pope III, PhDMary Lou Fulton Professor of Economics

Brigham Young University

International Sustainable Development SchoolTraining for Sustainability

2017: Air QualityOctober 30-November 3, 2017

What do we breathe?

Pure Air--nitrogen (78%), oxygen (21%), argon . . .

+Air pollutants, including:➢Various gaseous pollutants (SO2, NO2, CO, O3 . . . )

➢Particulate matter:Course particles (> 2.5 µm in diameter)

PM2.5—Fine particles (< 2.5 µm in diameter)

➢Other air toxics

How small are fine particles?

Human Hair

(60 mm diameter)

PM10

(10 mm)

PM2.5

(2.5 mm)

Magnified ambient particles (www.nasa.gov/vision/earth/environment)

Beijing, ChinaIndia--Lucknow, Chandigarh, Jaipur

Salt Lake City, UtahIndia--Agra (Taj Mahal)Medellin, Colombia

1st Controversy:

Was London smog romantic or deadly?

Peter Ellenshaw paintings from Mary Poppins

Claude Monet,

Houses of Parliament,

London,1903

http://upload.wikimedia.org/wikipedia/commons/9/97/Palace_of_Westminster,_London_-_Feb_2007.jpg

Old King Coal and the Fog Demon brings asthma, pneumonia, pleurisy and bronchitis to London.

Cartoon from British humor magazine Punch, 1880.

Image: Public Domain Review

Romantic vs. deadly controversy largely resolved with three well-documented air pollution episodes.

Dec. 5-9, 1952: London--1000’s of excess deaths

Dec. 1-5, 1930: Meuse Valley, Belgium60 deaths (10x expected)

Oct. 27-31, 1948: Donora, PA20 deaths, ½ the town’s population fell ill

Respiratory and cardiovascular disease and death

London Fog Episode, Dec. 1952

From: Brimblecombe P. The Big Smoke, Methuen 1987

David Bates, MDSt. BartholomewMcGill U, UBC

Killer Smog (and related research)

Public Policy Results1955-1967: Air pollution control

acts

1967, 1970: Clean Air Act, EPAMajor Amendments, National

Environmental Policy Act

1977 & 1990: Major Amendments

to Clean Air Act

1980’s: Elimination of

extreme “Killer Smog” episodes & Improved air quality

1930: Meuse Valley, Belgium

1948: Donora, PA

1952: London, England

National Ambient Air Quality Standards

1st Controversy:

Were extreme smog episodes romantic or deadly?

Answer: Deadly

2nd Controversy:

Can short-term exposure to moderate levels of pollution hurt us?

Utah Valley, 1980s

• Winter inversions trap local pollution

• Natural test chamber

• Local Steel mill contributed ~50% PM2.5

• Shut down July 1986-August 1987• Natural Experiment

Geneva Steel, Utah Valley, 1989 (PM10 = 150 mg/m3)

Air pollution workshop participants in front of Geneva Steel, March 19-20, 1992

Joel SchwartzBart OstroArden PopeJane KoenigJack SpenglerFred LipfertSverre VedalDoug DockeryDavid Bates

Utah Valley, 1989, (PM10 = 220 mg/m3) There are 250,000+ people breathing down there—including asthmatic children and elderly with CV and COPD. Does this pollution affect their health?

mg/m

3/N

um

bers

of A

dm

issio

ns

0

50

100

150

200

250

300

PM10 concentrations Children's respiratory hospital admissions

Mean PM10

levels forMonthsIncluded

Mean HighPM

10


PneumoniaandPleurisy

Bronchitisand Asthma

Total

Children's Respiratory Hospital AdmissionsFall and Winter Months, Utah Valley

Sources: Pope. Am J Pub Health.1989; Pope. Arch Environ Health. 1991

When the steel mill was open, total children’s hospital admissions for respiratory conditions approx. doubled.

mg

/m3/N

um

be

rs o

f A

dm

issio

ns

0

50

100

150

200

250

300

PM10 concentrations Children's respiratory hospital admissions

Mean PM10


Mean HighPM

10


PneumoniaandPleurisy

Bronchitisand Asthma

Total

Children's Respiratory Hospital AdmissionsFall and Winter Months, Utah Valley

Sources: Pope. Am J Pub Health.1989; Pope. Arch Environ Health. 1991

Mill

Open

Mill

Closed

Time-series studies take advantage of highly variable air pollution levels

98 99 00 01 02 03 04 05 06 07 08 09 10

0

10

20

30

40

50

60

70

80

90

100

98 99 00 01 02 03 04 05 06 07 08 09 10

0

10

20

30

40

50

60

70

80

90

100

PM2.5 concentrations January 1 1998-December 12 2009. Black dots, 24-hr PM2.5; Red line, 30-day moving average PM2.5;

Green line, 1-yr moving average PM2.5.

Utah Valley (Lindon Monitor)

g/m

3

Salt Lake Valley (Hawthorn Monitor)

g/m

3

Salt Lake Valley (Hawthorn Monitor)

Daily changes in air pollution daily death counts

Time (days)

# o

f D

eath

s

Utah Valley

Poisson Regression

Count data (non-negative integer values). Counts of independent and

random occurrences classically modeled as being generated by a Poisson

process with a Poisson distribution:

Prob (Y = r) = e(-λ)

Note: λ = mean and variance. If λ is constant across time, we have a

stationary Poisson process. If λ changes over time due to changes in

pollution (P), time trends, temperature, etc., this non-stationary Poisson

process can model as:

ln λt = α + β(w0Pt + w1Pt-1 + w2Pt-2 + . . .) + s1(t) + s2(tempt) + . . .

λr

r!

How to construct

the lag structure? (MA, PDL, etc.)

How aggressive do you

fit time? (harmonics vs GAMs, df, span, loess, cubic spline, etc.)

How to control for

weather? (smooths of temp & RH, synoptic weather, etc.)

Embedded Statistical modeling controversies

Also: How to combine or integrate information from multiple cities

Joel Schwartz, PhDHarvard

Scott Zeger, PhDJohns Hopkins

% in

cre

ase

in

mo

rta

lity

0

1

2

3

Estimates frommeta analysis

Estimates from Multicity studies

29 c

itie

s(L

evy e

t al. 2

000)

GA

M-b

ased s

tudie

s(S

tieb e

t al. 2

002,

2003)

Unadju

ste

d(A

nders

on e

t al. 2

005)

6 U

.S.

citie

s(K

lem

m a

nd M

ason 2

003)

8 C

anadia

n c

itie

s(B

urn

ett

and G

old

berg

2003)

9 C

alif

orn

ian c

itie

s(O

str

o e

t al. 2

006)

10 U

.S c

itie

s(S

chw

art

z 2

000,

2003)

14 U

.S c

itie

s,

case-c

rossover

(Schw

art

z 2

004)

NM

MA

PS

, 20-1

00 U

.S.

citie

s(D

om

inic

i et

al. 2

003)

AP

HE

A-2

, 15-2

9 E

uro

pean c

itie

s(K

ats

ouyanni et

al. 2

003)

9 F

rench c

itie

s(L

e T

ert

re e

t al. 2

002)

13 J

apanese c

itie

s(O

mori e

t al. 2

003)

Non G

AM

-based s

tudie

s(S

tieb e

t al. 2

002,

2003)

Public

ation b

ias a

dju

ste

d

(Anders

on e

t al. 2

005)

7 K

ore

an c

itie

s(L

ee e

t al. 2

000)

20

g/m

3 P

M1

0

20

g/m

3 P

M1

0

20

g/m

3 P

M1

0

20

g/m

3 P

M1

0

20

g/m

3 P

M1

0

10

g/m

3 P

M2.5

20

g/m

3 P

M1

0

10

g/m

3 P

M2.5

10

g/m

3 P

M2.5

20

g/m

3 P

M1

0

20

g/m

3 P

M1

0

20

g/m

3 P

M1

0

20

g/m

3 B

S

40

g/m

3 T

SP

20

g/m

3 S

PM

Revie

w o

f A

sia

n L

it.-

-8 s

tudie

s(H

EI

Report

, T

able

TS

2)

20

g/m

3 P

M1

0

20

g/m

3 P

M1

0

20

g/m

3 P

M1

0

Estimates frommeta analysisfrom Asian Lit

PA

PA

Stu

die

s--

4 s

tudie

s(H

EI

Report

, T

able

TS

2)

Asia

n L

it.

incorp

ora

ting

PA

PA

stu

die

s(H

EI

Report

, T

able

TS

2)

18 L

atin A

m.

stu

die

s

(PA

HO

2005)

20

g/m

3 P

M1

0

Daily time-series studies ***of over 200 cities***

Jonathan Samet, MDJohns Hopkins, USC

Klea Katsouyanni, PhDU of Athens, King’s College London

Short-term changes in air pollution exposure are associated with:

• Daily death counts (respiratory and cardiovascular)

• Hospitalizations

• Lung function

• Symptoms of respiratory illness

• School absences

• Ischemic heart disease

• Etc.

3rd Controversy:

Can long-term exposures contribute to significant disease and loss of life?

2nd Controversy:Can short-term exposure to moderate levels of pollution hurt us?Answer: Yes

An Association Between Air Pollution andMortality in Six U.S. Cities

1993

Dockery DW, Pope CA III, Xu X, Spengler JD,Ware JH, Fay ME, Ferris BG Jr, Speizer FE.

Methods:

➢14-16 yr prospective follow-up of 8,111 adults living in

six U.S. cities.

➢Monitoring of TSP PM10, PM2.5, SO4, H+, SO2, NO2, O3 .

➢Data analyzed using survival analysis, including

Cox Proportional Hazards Models.

➢Controlled for individual differences in: age, sex,

smoking, BMI, education, occupational exposure.

Doug Dockery, ScDHarvard

Frank Speizer, ScDHarvard

http://content.nejm.org/

Average

Polluted

cities

Highly

Polluted

cities

Clean

cities

Particulate Air Pollution as a Predictor of Mortality in a Prospective Study of U.S. Adults

Pope CA III, Thun MJ, Namboodiri MM,

Dockery DW, Evans JS, Speizer FE, Heath CW Jr.

1995

Methods: Linked and analyzed ambient air pollution data from 51-151 U.S. metro areas with risk factor data for over 500,000 adults enrolled in the ACS-CPSII cohort.

Eugenia Calle, PhD

ACS

Michael Thun, MD

ACS

Susan Gapstur, PhD

ACS

25 July 1997

In 1997, U.S. EPA proposed national ambient air quality standards for PM2.5.

Legal challenges by various industry groups(Whitman v. Am. Trucking 531 U.S. 457)

Calls for independent validation and reanalysis

Dan Krewski

Rick BurnettMark Goldbergand 28 others

➢ Formal audit of data➢ Reproduce published

results➢ Conduct robustness

and sensitivity analysis

Confirmed originally reported results.

Legal uncertainty largely

resolved with 2001

unanimous ruling by the

U.S. Supreme Court.

Cox Proportional Hazards Survival Model

Cohort studies of outdoor air pollution have commonly used the CPH Model

to relate survival experience to exposure while simultaneously controlling for

other well known mortality risk factors. The model has the form

)()()( )(0

)()( txexptt l

i

Tll

i

Hazard function

or instantaneous

probability of

death for the ith

subject in the lth

strata.

Baseline

hazard

function,

common to all

subjects within a strata.

Regression equation that

modulates the baseline

hazard. The vector Xi(l)

contains the risk factor

information related to the hazard function by the

regression vector β which

can vary in time.

Extended the basic Cox PH model allow random effects,

spatial autocorrelation, and semi-non-parametric spacial moothing.

More

statistical

modeling

controversies

Richard Burnett, PhdHealth Canada/U. Ottawa

http://jama.ama-assn.org/

➢ 60,925,443 Medicare beneficiaries➢ Followed up from 2000-2012➢ 460,310,521 person-yrs follow-up

10 µg/m3 increase in PM2.5

7.3% (95% CI 7.1-7.5)increase in all-cause mortality

%

0

5

10

15

20

25

30

All-cause mortality Cardiovascular or Circulatory disease mortality

Jerrett et al. 2017

(alternative measures of PM2.5)

High-quality models

(lowest AIC) P

ope e

t al. 1

995

Kre

wski et

al. 2

000

Pope e

t al. 2

002

Kre

wski et

al. 2

009

Pope e

t al. 2

015

Enstr

om

2017

Jerr

ett

et

al. 2

009

Pope e

t al. 1

995

Kre

wski et

al. 2

000

Pope e

t al. 2

002

Pope e

t al. 2

004

Kre

wski et

al. 2

009

Jerr

ett

et

al. 2

009

Pope e

t al. 2

015

Relatively high exposure misclassification

(Remote sensing,no ground-based data)

[More subject/exposure mismatching]

(HEI Independent

reanalyis)

**

*

*

*

*

*

*

*

**

*

*

*

*

* *

Hoek e

t al. 2

013

Hoek e

t al. 2

013

Di et

al. 2

017

Harvard Six-Cities StudyDockery et al. New England

Journal of Medicine (NEJM), 1993

ACS CPS-II Cohort StudyPope, et al. Am J Respir Crit

Care Med (AJRCCM), 1995

Independent Re-analyses of Harvard Six-Cities and ACS CPS-II StudiesKrewski et al. HEI Special Report , 2000; J Tox Enviro Health, Special Issue, 2003➢3-yr reanalysis by a team of 31 independent researchers with oversight from a 9-member expert panel and peer review by a special panel of the HEI Health Review Committee.➢Included full data access that insured the privacy and confidentiality of research participants.➢Reanalyses include data audits, full replication and validation, and extensive sensitivity analyses.

Extended analyses ofHarvard Six-Cities studyLaden et al. AJRCCM, 2006Schwartz et al. EHP, 2008Lepeule et al. EHP, 2012

Extended analyses of ACS CPS-II studyPope et al. JAMA, 2002; Pope et al. Circulation, 2004; Jerrett et al.Epidemiology, 2005; Krewski et al. HEI Rep. 2009; Jerrett et al. NEJM,2009; Smith et al. Lancet, 2009; Turner et al. AJRCCM, 2011; Jerrettet al. AJRCCM, 2013; Pope et al. Circ. Res, 2015; Jerrett et al. EHP, 2017

Replicative studies in many (17+) other cohorts: Gehring et al. (German Women) Epi, 2006; Miller et al. (Women’s Health Initiative) NEJM, 2007; Beelen et al. (Netherlands) EHP, 2008; Zeger et al. (U.S. National Medicare) EHP, 2008; Puett et al. (Nurses Health Study) EHP, 2009; Puett et al. (Health Professionals) EHP, 2011; Hart et al. (U.S. Truckers) AJRCCM, 2011; Lipsett et al. (California Teachers) AJRCCM, 2011; Gan et al. (Vancouver) EHP, 2011; Cao et al. (China) J Hazard Mater. 2011; Zhang et al. (China) PLoS One, 2012; Crouse et al. (Canadian ) EHP, 2012; Hales et al. (New Zealand) J Epi Com Health, 2012; Cesaroni et al. (Rome) EHP, 2013; Beelen et al (22 European cohorts) Lancet, 2014; Kioumourtzoglou et al. (U.S. Medicare) EHP, 2016; Thurston et al. (NIH-AARP Diet and Health Cohort) EHP, 2016. Di et al. (U.S. Medicare) NEJM, 2017;

Sept. 26, 2017

Key estimated equations:

Mortality or

Life expectancy

for city j.

Indicator variable

equal to 1 for

locations North

of Huai River line

Polynomial

in degrees

North of Huai

River line

Other demographic

and city characteristics

that may effect mortality

Or estimate 2a as the first step in a two stage least-squares (2SLS) and

then estimated 2c above as the second stage equation.

4th Controversy:

So does reducing air pollution improve health and reduce mortality?

3rd Controversy:

Can long-term exposures contribute to significant disease and loss of life?

Answer: Yes

April 2016

Kiros T. Burhane, PhD USC

http://jama.ama-assn.org/

Reduction in fine particulate air pollution:Extended follow-up of the Harvard Six Cities Study(AJRCCM 2006)

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

0 5 10 15 20 25 30 35

PM2.5 (mg/m3)

Mo

rtali

ty R

isk R

ati

o

SteubenvilleTopeka

Watertown

Kingston

St. Louis

Portage

Francine Laden, ScDHarvard


Doug Dockery,ScDHarvard

Frank Speizer, MDHarvard

Fine-Particulate Air Pollution and Life Expectancy in the United States

C. Arden Pope, III, Ph.D., Majid Ezzati, Ph.D., and Douglas W. Dockery, Sc.D.

January 22, 2009

Majid Ezzati, PhDImperial College London

Matching PM2.5 data for

1979-1983 and 1999-2000 in51 Metro Areas

Life Expectancy data for1978-1982 and 1997-2001 in

211 counties in 51 Metro areas

Evaluate changes in Life

Expectancy with changes inPM2.5 for the 2-decade period

of approximately 1980-2000.

Francesca Dominici, PhDHarvard


10 µg/m3 decrease in PM2.5 associated with a one year increase in life expectancy.

This increase in life expectancy persisted even after controlling for

socio-economic, demographic, or smoking variables

http://content.nejm.org/content/vol360/issue4/images/large/10t2.jpeg

4th Controversy:

So does reducing air pollution improve health and reduce mortality?

Answer: Yes

5th Controversy:

Does a safe threshold even exist?

Ambient Concentrations ( g/m3)

$

CT

CM

Marginal HealthCosts of Pollution

He

alth

Eff

ect

Health Effect

U.S. CAA requires the EPA to set air quality standards that “are requisite to protect the public health with an adequate margin of safety.”

British Smoke

0 200 400 600 800 1000 1200 1400

Daily

Dea

ths

260

280

300

320

340

360

380

London

Schwartz and Marcus. Am J Epidemiology 1990

Early analyses of concentration-response function.

Used London mortality data for 14 winters

C-R function less steep at higher concentrations

No evidence of a threshold


Bart Ostro, PhDUC Davis

PM10

10 20 30 40 50 60 70 80 90

Rela

tive R

isk o

f D

ea

th

0.98

1.00

1.02

1.04

1.06

1.08

1.10

1.12

TSP

60 70 80 90 100 110 120 130

Rela

tive

Ris

k o

f D

ea

th

0.995

1.000

1.005

1.010

1.015

1.020

1.025

PM10

10 15 20 25 30 35 40 45 50

Rela

tive R

isk o

f D

ea

th

0.99

1.00

1.01

1.02

1.03

1.04

1.05

TSP

40 60 80 100 120 140

Rela

tive R

isk o

f D

ea

th

0.99

1.00

1.01

1.02

1.03

1.04

PM10

40 60 80 100 120 140

Rela

tive R

isk o

f D

ea

th

0.98

1.00

1.02

1.04

1.06

1.08

1.10

1.12

1.14

British Smoke

0 200 400 600 800 1000 1200 1400

Daily

Dea

ths

260

280

300

320

340

360

380

LondonA DetroitB

St. LouisC D Utah Valley

E Philadelphia F Sao Paulo

0 20 40 60 80 100

% in

cre

ase

in

de

ath

s

0

2

4

6

8

0 20 40 60 80 100

% in

cre

ase

in

de

ath

s

0

2

4

6

8

0 20 40 60 80 100

% in

cre

ase

in

de

ath

s

0

2

4

6

8

0 20 40 60 80 100 120 140 160 180 200 220%

in

cre

ase

in

de

ath

s

0

2

4

6

8

PM10

(mg/m3)

0 20 40 60 80 100

% in

cre

ase

in

de

ath

s

0

2

4

6

8 10 U.S. Cities

(Schwartz and Zanobetti 2000)a 8 Spanish Cities

(Schwartz et al. 2001)b

20 U.S. Cities

(Daniels et al. 2000;

Dominici et al. 2003)

c d 88 U.S. Cities

(Dominici et al. 2002;

Dominici et al. 2003)

e 22 European Cities

(Samoli et al. 2005)

Figure 1. Selected concentration-response relationships estimated fromvarious multi-city daily time-series mortality studies (approximate adaptationsfrom original publications re-scaled for comparison purposes).

BS (mg/m3)

PM10

(mg/m3) PM

10 (mg/m

3)

PM10

(mg/m3)

5 10 15 20 25 30

0.8

0.9

1.0

1.1

1.2

1.3

1.4

P

T W

L

H

S

p t

w

l

h

s

5 10 15 20 25 30

650

700

750

800

850

900

950

1000

1050

U.S. cross-sectional mortality Harvard Six-cities

(Laden et al. 2006)

5 10 15 20 25 30

Ad

juste

d m

ort

alit

y r

ela

tive r

isk

0.8

0.9

1.0

1.1

1.2

1.3

1.4

5 10 15 20 25 30

FE

V1 <

80

% o

f p

red

icte

d (

%)

0

2

4

6

8

10

12 dc

a b

Figure 2. Selected concentration-response relationships estimated fromvarious studies of long-term exposure (approximate adaptations fromoriginal publications re-scaled for comparison purposes).

PM2.5

(mg/m3)PM

2.5 (mg/m

3)

ACS cohort

(Pope et al. 2002)Children's Lung Growth

(Gauderman et al. 2004)

19

80

ad

juste

d m

ort

alit

y(d

ea

ths/y

r/1

00

,00

0)

Ad

juste

d m

ort

alit

y r

ela

tive r

isk

PM2.5

(mg/m3) PM

2.5 (mg/m

3)

Period 1 (upper case)

Period 2 (lower case)

All cause

Cardiopulmonary

Lung Cancer

All other

Cardiopulmonary Mortality(Pope et al. JAMA 2002)

5th Controversy:

Does a safe threshold even exist?

Answer: No. Near linear C-R.

6th Controversy:

If PM2.5 effects are this big, and near linear,

why isn’t everyone who smokes dead?

0 60 120 180 240

Ad

jus

ted

Re

lati

ve

Ris

k

1.0

1.5

2.0

estimated daily dose of PM2.5

, mg

18-22cigs/day

Pack-a-day smoker:

RR ~ 2

Daily inhaled dose ~ 240 mg

Live in polluted city or

With smoking spouse

RR ~ 1.15 – 1.35

Daily inhaled dose ~ 0.2–1.0 mg

Estimated daily dose assumes:

• Inhalation rate of 18 m3/day

• 12 mg/cig

30 µg/m3 of mean PM2.5 X

18 m3/day inhalation rate =540 µg or 0.54 mg daily dose of PM2.5

12 mg/cig X 20 cigs = daily dose of 240 mg PM2.5

0 60 120 180 240 300

Ad

juste

d R

ela

tive R

isk

1.0

1.5

2.0

2.5

<3cigs/day


, mg

23+cigs/day

8-12cigs/day

13-17cigs/day

18-22cigs/day

4-7cigs/day

Figure A. Adjusted relative

risks (and 95% CIs) of IHD (light gray), CVD (dark gray), and CPD (black)

mortality plotted over estimated daily dose of

PM2.5 from different increments of current cigarette smoking.

Pope, Burnett, Krewski, et al. 2009.

Estimated daily dose assumes:• Inhalation rate of 18 m3/day • 12 mg/cigarette

0 60 120 180 240 300

Ad

jus

ted

Re

lati

ve

Ris

k

1.0

1.5

2.0

2.5

<3cigs/day


, mg

23+cigs/day

8-12cigs/day

13-17cigs/day

18-22cigs/day

4-7cigs/day

Pope, Burnett, Krewski, et al. 2009.Figure 1. Adjusted relative




Diamonds represent comparable mortality risk

estimates for PM2.5 from air pollution. Stars represent comparable pooled relative

risk estimates associated with SHS exposure from

the 2006 Surgeon General’s report and from the INTERHEART study.


0.1 1.0 10.0 100.0

Ad

juste

d R

ela

tive R

isk

1.0

1.5

2.0

2.5


, mg

Exposure from

Second hand cigarette smoke: Stars, from 2006 Surgeon General Report and INTERHEART studyAnd air pollution: Hex, from Womens Health Initiative cohort Diamonds, from ACS cohort Triangles, Harvard Six Cities cohort

Exposure from smoking<3, 4-7, 8-12, 13-17, 18-22, and 23+

cigarettes/day

Figure 2. Adjusted relative

risks (and 95% CIs) of ischemic heart disease (light gray), cardiovascular

(dark gray), and cardiopulmonary (black)

mortality plotted over baseline estimated daily dose (using a log scale) of

PM2.5 from current cigarette smoking (relative

to never smokers), SHS, and air pollution.



6th Controversy:

If PM2.5 effects are this big, and near linear, why isn’t everyone

who smokes dead?

Answer: Not linear—diminishing marginal effects.

7th Controversy:

Are these health effects biologically plausible?

2004.

RR

(9

5%

CI)

0.65

0.70

0.75

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

1.20

1.25

1.30

1.35

1.40A

ll C

ard

iova

scu

lar

plu

s D

iab

ete

s

Isch

em

ic h

ea

rtd

ise

ase

Dysrh

yth

mia

s,H

ea

rtfa

ilure

, C

ard

iac a

rre

st

Hyp

ert

en

siv

ed

ise

ase

Oth

er

Ath

ero

scle

rosis

,a

ort

ic a

ne

ury

sm

s

Ce

reb

ro-

va

scu

lar

Oth

er

Ca

rdio

-va

scu

lar

Dia

be

tes

Re

sp

ira

tory

Dis

ea

se

s

CO

PD

an

da

llie

d c

on

ditio

ns

Pn

eu

mo

nia

,In

flu

en

za

All

oth

er

resp

ira

tory

Figure 1. Adjusted relative risk ratios for cardiovascular and respiratory mortality associated with

a 10 mg/m3 change in PM

2.5 for 1979-1983, 1999-2000, and the average of the two periods.

(Relative size of the dots correspond to the relative number of deaths for each cause.)

John Godleski, MD

Harvard

Biological mechanisms include:➢ Pulmonary and systemic inflammation➢ Accelerated atherosclerosis➢ Altered cardiac autonomic function

Eugenia Calle, Phd

ACS

Brook, Rajagopalan, Pope, et al. 2011

AHA Scientific Statement, PM and CVD

Robert Brook, MDU of Michigan

Sanjay Rajagopalan, MDUH Cleveland Medical

Fine particulate

exposure(from smoking or air pollution)

↓

Pulmonary and

systemic inflammation

and oxidative stress

(along with blood lipids)

↓

Endothelial

injury/dysfunction

↓

Progression and

destabilization of

atherosclerotic plaques

Consistent with EPI evidence of:

➢ Coronary artery disease➢ Ischemic heart disease events➢ Subsequent heart failure➢ Ischemic strokes➢ Deep vein thrombosis

(and potential pulmonary embolism)

2016Aruni Bhatnagar, PhD FAHAU of Louisville

Tim O’Toole, PhDU of Louisville

Enroll research subjects including 72 young, healthy, non-smoking adults from BYU/Provo. (Note DataRAM PM2.5 monitor).

Multiple blood draws during relativelyclean and polluted periods over 3 yrs.

Process blood, ship to UofL.

Microparticles and immune cells quantified using a multi-laser flow cytometer (Becton Dickinson LSR II) at UofL

An array of 42 human cytokines and an array of 2 markers of endothelial adhesion (sICAM-1 and sVCAM-1) were measured from frozen plasma aliquots by analytic services at Eve Technologies(Calgary, Alberta, Canada) using multiplexing laser bead technology.

Statistical Analysis

• Fixed-effects regression models

• Subject-mean-adjusted regression

• Graphical analysis

• Sensitivity analysis

1/6 1/13 1/20 1/27 2/3 2/10 2/17 2/24 3/3 3/10 3/17

PM

2.5 (

g/m

3)

0

10

20

30

40

50

60

70

80

90

100

110

120

130

Lindon 1-d FRMNorth Provo 1-d FRMSpanish Fork 1-d FRMLindon 24-h Real timeNorth Provo 24-h Real timeBlood Draws, Subs 1-12

Blood Draws, Subs 13-24

2013

1/5 1/12 1/19 1/26 2/2 2/9 2/16 2/23 3/2 3/9 3/16

PM

2.5 (

g/m

3)

0

10

20

30

40

50

60

70

80

90

100

110

120

130


Blood Draws, Subs 13-24FOB 24-hr Real time

Blood-draw room 24-hr

2014

12/7 12/14 12/21 12/28 1/4 1/11 1/18 1/25 2/1 2/8 2/15 2/22 3/1 3/8 3/15 3/22 3/29 4/5

PM

2.5 (

g/m

3)

0

10

20

30

40

50

60

70

80

90

100

110

120

130


Blood Draws, Subs 13-24

FOB 24-hr Real timeBlood-draw room 24-hr

2014/2015

Figure 1. PM2.5

concentrations and

blood-draw dates

plotted during study

periods.

Elevated

circulating

endothelial

microparticles

indicative of

endothelial cell

apoptosis and

endothelial

injury.

Elevated circulating monocytes and T,

but not B, lymphocytes—Suggestive

of a non-specific or innate immune

response and not a specific adaptive

response involving production of

antibodies targeting specific antigens.

Weaker but sig. association with

platelet-monocyte aggregates

%

-8

-6

-4

-2

0

2

4

6

8

10

12

14

16

TN

F

sIC

AM

-1

MC

P-1

IL-8

Fra

cta

lkin

e

MIP

-1

MIP

-1

IP-1

0

sV

CA

M-1

IL-6

IL-1

0

IL-1

IL-9

IL-1

5

IL-1

RA

IL-1

3

IL-1

2P

70

G-C

SF

Eo

taxi

n-1

IL-5

IL-1

TN

F

MC

p-3

IL-1

2P

40

FG

F-2

TG

F

GM

-CS

F

IL-1

7A

IL-2

IL-7

IFN

y

IL-4

PD

GF

-BB

Flt-3

L

IL-1

8

MD

C

IFN

2

IL-3

VE

GF

-A

GR

O

RA

NT

ES

PD

GF

-AA

sC

D4

0L

EG

F

Figure 3. Percent change (and 95% CIs) in analyte per 10 g/m3 increase in PM

2.5 relative to mean value

of analyte. Estimates come from subject-mean adjusted regressions. The results are ordered from left to

right based on t-values--resulting in the most statistically signifiant possitive associations being on the left

and the most statistially significant negative associations being on the right.

Statistically significant even when

using the Bonferroni correction for

multiple testing of 44 analytes (P<0.05/44)

Statistical interpretation

%

-8

-6

-4

-2

0

2

4

6

8

10

12

14

16T

NF

sIC

AM

-1

MC

P-1

IL-8

Fra

cta

lkin

e

MIP

-1

MIP

-1

IP-1

0

sV

CA

M-1

IL-6

IL-1

0

IL-1

IL-9

IL-1

5

IL-1

RA

IL-1

3

IL-1

2P

70

G-C

SF

Eo

taxi

n-1

IL-5

IL-1

TN

F

MC

p-3

IL-1

2P

40

FG

F-2

TG

F

GM

-CS

F

IL-1

7A

IL-2

IL-7

IFN

y

IL-4

PD

GF

-BB

Flt-3

L

IL-1

8

MD

C

IFN

2

IL-3

VE

GF

-A

GR

O

RA

NT

ES

PD

GF

-AA

sC

D4

0L

EG

F

Figure 3. Percent change (and 95% CIs) in analyte per 10 g/m3 increase in PM

2.5 relative to mean value

of analyte. Estimates come from subject-mean adjusted regressions. The results are ordered from left to

right based on t-values--resulting in the most statistically signifiant possitive associations being on the left

and the most statistially significant negative associations being on the right.

Increase in proinflammatory/

anti-angiogenic cytokines (TNFα,

monocyte chemoattractant protein 1,

IL-8, macrophage inflammatory

protein 1α/β, interferon γ-induced

protein 10)

Suppressed cytokines/ growth

factors that are potent

pro-angiogenic factors,

including: epidermal growth

factor, CD40 ligand, platelet-

derived growth factor, RANTES,

growth-regulated protein alpha,

and vascular endothelial growth

factor.

Anti-angiogenic plasma profile

Elevated intercellular adhesion molecule 1

and vascular cellular adhesion molecule 1.

7th Controversy:

Are these health effects biologically plausible?

Answer: There are plausible biological mechanisms.

8th Controversy:

Aren’t air pollution health effects just small compared to other more important risk factors.

The Global Burden of Disease 2010

Bre

ath

ing

Co

nta

min

ants

Christopher Murray, MDU of Washington, IHME

Aaron Cohen, DSc.HEI, IHME

http://www.google.com/url?sa=i&rct=j&q=THe+Lancet&source=images&cd=&docid=NN0YMZtOHkao5M&tbnid=w3lPsvY3e2sAlM:&ved=0CAUQjRw&url=http://www.iepfpd.org/epf-news/96/the-lancet-publishes-series-on-global-health/&ei=rdAnUc2-FKKxiwLat4CIDw&bvm=bv.42768644,d.cGE&psig=AFQjCNE8HPeyA0SvC-xnFBh4cYWpHMSxng&ust=1361650217787641


Figure 1. Global DALYs attributable to risk factors for (B) women, and (A) men in 2015.

DALYs=disability adjusted life years.

In 2015 air pollution was estimated to be the 4th to 6th largest risk factor contributing to GBD for both men and women.



Breathing contaminants contributes to global burden of disease (GBD)

Number of attributable deaths

Tobacco Smoking 6.4 mil.

Second Hand Smoke 0.9 mil.

PM2.5 air pollution 4.2 mil.

Household air pollution from solid fuels 2.9 mil.

Ambient Ozone 0.2 mil.


8th Controversy:

Aren’t air pollution health effects just small compared to other more important risk factors.

Answer: No. The effects of air pollution as substantial.

9th Controversy:

Cleaning up air pollution costs too much and hurts our economy.

Clean versus

polluted air is

among our

economic

choices.

➢ Clean air is an economic good that contributes to human

well-being, human capital, and positive environmental

amenities.

➢ The “production” of clean air can contribute to economic

prosperity, human well being, and improved public health.

Medellin

Changes in Economic Indicators and Pollutant Emissions 1970-2015. Adapted from Samet et al. NEJM March 1, 2017.

Gross domestic product

Vehicle miles traveled

Population

Energy consumption

CO2 emissions

Aggregate air pollutionemissions (6 common pol.)

1970CAA

&EPA

U.S. EPA March 2011

10th Controversy: How much evidence is needed before efforts to have clean air are no longer controversial?

Economics Principles ofAir Pollution Management

Over London by Rail, 1870

Gustave DoréDepicts the congested and pollutedIndustrial environment of 1870 London

Classical Economics

• Adam Smith (Scottish social philosopher and political economist), author of Wealth of Nations (1776), free markets,

competition, and the metaphor of the

“invisible hand”.

• Doctrine of “Laissez-faire”

• What about air pollution? Smells like money to me!

Began to lose our Faith in the doctrine of Laissez-fair

Dec. 5-9, 1952: London--1000’s of excess deaths

Dec. 1-5, 1930: Meuse Valley, Belgium60 deaths (10x expected)

Oct. 27-31, 1948: Donora, PA20 deaths, ½ the town’s population fell ill

Respiratory and cardiovascular disease and death

Loss of Faith in the doctrine of Laissez-faire

• No longer did air pollution “smell like money” but it smelled like something unhealthy.

• In the UK, US, and elsewhere public policy efforts to clean up the air and eliminate the “Killer Smog Episodes” began (Clean air act).

• There was success at eliminating or reducing the extreme air pollution episodes but air pollution remained and we have learned that even moderate air pollution had adverse health effects.


$

CT

CM



$

Marginal Costof Abatement

Marginal Health Costof Pollution

CT C* C

M


$



CT C* C

M

Management approach 1—Do nothing


$



CT C* C

M

DEAD WEIGHT LOSS(due to over abatement)

Management approach 2—Abate pollution at or below threshold


$



CT C* C

M

Re

gula

tory

act

ion

1 (

ban

co

al/w

oo

d b

urn

ing

for s

pac

e h

eat

ing)

Re

gula

tory

act

ion

2 (

stag

e I

auto

em

issi

on c

on

tro

ls)

Re

gula

tory

act

ion

3 (

coal

po

we

r pla

nt c

on

tro

ls)

Re

gula

tory

act

ion

5

(sta

ge II

au

to e

mis

sion

co

ntr

ols

)

Re

gula

tory

act

ion

4 (

ste

el

mil

l/sm

elte

r em

issi

on

con

tro

ls)

RA 6 (Dieselemission controls)

Management approach 3—Use regulatory actions and B/C criteria


$



CT C* C

M

Re

gula

tory

act

ion

1 (

ban

co

al/w

oo

d b

urn

ing

for s

pac

e h

eat

ing)

Re

gula

tory

act

ion

2 (

stag

e I

auto

em

issi

on c

on

tro

ls)

Re

gula

tory

act

ion

3 (

coal

po

we

r pla

nt c

on

tro

ls)

Re

gula

tory

act

ion

5

(sta

ge II

au

to e

mis

sion

co

ntr

ols

)

Re

gula

tory

act

ion

4 (

ste

el

mil

l/sm

elte

r em

issi

on

con

tro

ls)

RA 6 (Dieselemission controls)

Assumes regulatory management that is wise, competent, well-enforced, efficient, not over reaching,politically acceptable, etc.


$



CT C* C

M

Piqovian Tax rate or Price in Cap-and-Trade scheme.

Management approach 4 and 5—Use Pigovian Taxes or Cap-and Trade


$



CT C* C

M

Piqovian Tax rate or Price in Cap-and-Trade scheme.

Also assumes management and enforcement of the Piqovian Tax or the Cap-and-Trade scheme that is feasible, enforceable, politically acceptable, etc.

In Six-Cities study, adjusted relative risk of dying werealmost linearly associated with air pollution.

In ACS study, adjusted relative risk of dying were

almost linearly associated with air pollution.


$



C*


$


Marginal HealthCost of Pollution

C*

high estimate

median estimate

low estimate

CL C

H

0 60 120 180 240 300

Ad

jus

ted

Re

lati

ve

Ris

k

1.0

1.5

2.0

2.5

<3cigs/day


, mg

23+cigs/day

8-12cigs/day

13-17cigs/day

18-22cigs/day

4-7cigs/day


Figure 1. Adjusted relative




Diamonds represent comparable mortality risk

estimates for PM2.5 from air pollution. Stars represent comparable pooled relative

risk estimates associated with SHS exposure from

the 2006 Surgeon General’s report and from the INTERHEART study.


$

C* CH

Marginal Costsof Abatement


CNC

Pollution Abatement


$

C* CH



CNC

In 2007 and 2008 OMB estimates that the

largest benefits of ALL federal regulations were

attributable to controlling exposure to a single

air pollutant:

fine particulate matter (PM2.5).

Estimated benefits:

$18.8 to $167.4 billion/year

Estimated costs:

$7.3 billion per/year


$

C* CH



CNC

ER = 0.0063 * (PM2.5)

(Approximately from Hoek et al., 2013)

ER = 0.4 {1 – exp [-.03 (PM2.5)0.9 ] }

(Approximation based on functional form of the integrated risk function, Burnett et al. 2014).

Figure 2. Stylized analysis of pollution abatement for linear and supralinear C-R functions.

From:Pope, Cropper, Coggins, Cohen. JAWMA 2015

Fine-Particulate Air Pollution and Life Expectancy in the United States

C. Arden Pope, III, Ph.D., Majid Ezzati, Ph.D., and Douglas W. Dockery, Sc.D.

January 22, 2009

Matching PM2.5 data for1979-1983 and 1999-2000 in

51 Metro Areas

Life Expectancy data for

1978-1982 and 1997-2001 in 211 counties in 51 Metro areas

Evaluate changes in Life

Expectancy with changes in

PM2.5 for the 2-decade periodof approximately 1980-2000.


0 2 4 6 8 10 12 14

0

5

10

15

20

Reduction in PM2.5 (mg/m3)

Incr

eas

e in

inco

me

($

10

00

s)

Br = -0.027, p = 0.71

Tradeoffs between, air

pollution and life expectancy

in the U.S., 1980-2000.Pope, Ezzati, DockeryEnviron Res. 2015

Changes in Economic Indicators and Pollutant Emissions 1970-2015.Adapted from Samet et al. NEJM March 1, 2017.

GDP

Vehicle miles traveled

Population

Energy consumption

CO2 emissions

Aggregate air pollutionEmissions(6 common pol.)

1970CAA

&EPA

Clean versus

polluted air is

among our

economic

choices.

➢ Clean air is an economic good that contributes to human

well-being, human capital, and positive environmental

amenities.

➢ The “production” of clean air can contribute to economic

prosperity, human well being, and improved public health.

Medellin

Finally,

This stylized approach ignores various uncertainties and complications including:

➢Interactive multi-pollutants,

➢Issues of environmental justice,

➢How do efforts to reduce traditional air pollutants complement or diverge from efforts to address climate change and is there a reasonable way to integrate these efforts.

Thank you.

relationships between air quality, health and...

Documents