Acrolein and Adult Asthma in a Nationally Representative Sample of

the United States

B. Rey de Castro, Sc.D.Statistician

before the International Society of Exposure Science

Baltimore, MDOctober 24, 2011

National Center for Health Statistics

Office of Analysis & Epidemiology, Special Projects Branch

Acrolein

Aldehyde Hazardous Air Pollutant subject to Clean Air

Act

Ubiquitous

Combustion Tobacco Mobile sources, especially diesel Airports Wood heating & forest fires Industrial boilers

Indoor air pollutant Cooking Smoking

Ubiquitous

Largest industrial uses Synthesis of acrylic acid Biocide

Two biggest emitting facilities in Alvin and Diboll, TX

Next 8 biggest: IL, VA, NE, IA, WI, KS Top 10 responsible for 90 percent of TRI

emissions.

2005 TRI: Acrolein

Exposure

Inhalation Combustion by-products Cigarette smoke Cooking smoke

Food Heating carbohydrates, lipids, certain amino acids

Formed physiologically Oxidative stress Polyamine metabolism

Highly Potent Irritant

Acute and chronic (non-cancer) effects Respiratory congestion Eye, nose, throat Skin Especially sensitive

Asthmatics Allergy sufferers

1 2 3 4 5 6 7 80.00001

0.0001

0.001

0.01

0.1

1

10

100

1000 LC50 750

LOAEL 0.9

RfC 0.00002

NIOSH IDLH4.6

NIOSH STEL0.8

OSHA PELNIOSH REL

0.25

ACGIH CeilingEPA AEGL2 8h

0.23

EPA AEGL1 8h0.07

Log10 A

mbie

nt

Acro

lein

Concentr

ati

on [

mg/m

3]

Regulatory Ambient Exposure Levels

Ambient Measurement Very Difficult

Highly reactive Ambient formation

Even within samplers Sensitive to

Sampler preparation Sampler type Time elapsed from preparation to analysis

Inter-laboratory variability in analysis

Current Ambient Methods

US EPA TO-11a: canister sampler TO-15: cartridge sampler TO-15 superseding TO-11a Resolution: hours — days TO-15a still problematic Subject of ongoing improvement research

Near real-time monitor Recently developed Quantum cascade laser IR absorption

Therefore, no epidemiologic

research on acrolein

Alternative 1: Exposure Biomarkers

Urine Mercapturic acid metabolites Analytical methods recently developed at

CDC Poster here at ISES 2011: Abstract 1120986 By Udeni Alwis, Sc.D. uAlwis@cdc.gov

Not the subject of this talk

Alternative 2: Modeled Exposure

US EPA National-Scale Air Toxics Assessment 2005

Nationwide estimate of chronic inhalation exposure Census tract resolution

Hazardous air pollutants & diesel particulate matter

Diesel particulate matter Cancer and non-cancer health effects

NATA 2005

EPA says: Acrolein responsible for “about 75 percent of the

nationwide average non-cancer hazard” Remarkable for air toxic with no

epidemiology

Now that we have exposure estimates, what if we could gethealth effects data?

Nationwide Health Effects

National Health Interview Survey 2000 — 2009

Content Health conditions and behaviors Access to health services

Representative sample of United States , nationwide Non-institutionalized Civilian

Cross-sectional prevalence

National Health Interview Survey

Interview Face to face Computer-aided

Data N ~ 40,000 households (~87,000 individuals) annually Initiated in 1957

Multistage Population Sampling

Complex Survey Design

Cross-sectional Use of weighting, clustering, and

stratification Oversampling Variance estimation complicated

Special software: SUDAAN™ Taylor series linearization method (GEE)

NHIS 2000 — 2009

10 years NHIS data Adults 18 years-old and over Self-reported asthma attack in previous 12

months Has a doctor ever told you that you have asthma?

AND Have you had an asthma attack in the last 12 months?

Standard CDC definition for evaluating national asthma trends

NHIS Confidential Data

Aim: geographic merge with NATA 2005 Data not for public use

Geocoded NHIS subject residence Urban/rural residence

NCHS Research Data Centers (RDCs) Access non-public use data Confidential data merges Locations nationwide

NATA-NHIS Data Merge

Merge by

Census Tract

NATA: Acrolein Exposur

e

NHIS: Adult

Asthma

Merged NATA-NHIS Data

NATA 2005 & NHIS 2000-2009

Sample size: 209, 365 subjects 72.8 percent of 287,530 subjects

Census tracts: 14,936 22.6 percent of 66,029 tracts

Asthma attacks in last 12 months: 3.98 percent subjects

NATA 2005 & NHIS 2000—2009

White: 71.5 percent Male: 48.8 percent Age: ≥18 years-old Never smokers: 55.5 percent ≥High school graduate: 83.9 percent Insured: 83.7 percent Access to care: 85.3 percent Urban: 74.6 percent

Population-Weighted Outdoor Acrolein Exposure

[µg/m3]

Mean (SE) 3.34E-2 (3.94E-4)Geometric Mean (GSE)

2.27E-2 (2.43E-4)

Population-Weighted Outdoor Acrolein Exposure

[µg/m3]

Median (IQR)

2.45E-2 (3.11E-2)

5th Percentile

4.97E-3

10th 6.62E-325th 1.22E-275th 4.34E-290th 6.87E-295th 8.78E-2

Logistic Regression Model

Binary outcome: asthma attack last 12 months NHIS 2000 — 2009 Self-report

Predictor of interest: acrolein quintile NATA 2005 Inhalation exposure concentration at census tract

Potential Asthma Confounders

Race, sex, age, smoking, education, insurance coverage, access to healthcare, urban/rural residence, survey year, survey quarter

Based on prior NHIS research on asthma trends

Complex Survey Variance Estimation

Taylor series linearization (GEE) Survey sample weights 2000 — 2009 Indicators for survey stratum and PSU

pOR by Acrolein Quintile

1 2 3 4 50.80

0.90

1.00

1.10

1.20

1.30

Exposure Quintile

pO

R

Primary Result

At highest quintile of acrolein exposure 0.0551 – 0.457 µg/m3 pOR 1.11 [1.00:1.23] adult asthma

11 percent increase in adult asthma prevalence

Controlling for race, sex, age, smoking, education, insurance coverage, access to healthcare, urban/rural residence, survey year, survey quarter

Reference concentration (RfC) = 0.02 µg/m3

Stratified Analysis by Residence

Urban at highest quintile of acrolein exposure pOR 1.13 [1.00:1.29] adult asthma

Rural at highest quintile of acrolein exposure pOR 1.08 [0.80:1.44] adult asthma

Controlling for race, sex, age, smoking, education, insurance coverage, access to healthcare, survey year, survey quarter

Confounders

Statistically significant Race, sex, age, smoking, education, access to

healthcare, urban/rural residence, survey year Not statistically significant

Insurance coverage, survey quarter

38

Strengths

Inexpensive data collection and design Large sample National geographic coverage Census tract resolution Generalizable to US population

39

Limitations

Uncertainty of NATA exposure estimates Merge bias Cross-sectional Acrolein from indoor air, food Effect estimation in smaller areas severely

limited

Feasible to conduct national epidemiologic analysis with modeled

chronic exposure estimates for air toxics

First demonstration of acrolein’s adverse effect

on general population

Approaches to Acrolein Exposure Assessment

Exposure Assessment

Modeled

Biomarkers

Measurement

Acknowledgements

Jenifer Parker, Ph.D. Chief, NCHS OAE Special Projects Branch Merged EPA air quality data with

• NHIS 1986 — 2005• NHANES 1986 — 1994• National Hospital Discharge Survey 1999 — 2005

CDC Guest Researcher Program Research conducted in my spare time

2005 2006 2007 2008 2009 2010 2011 to October

19

0

50

100

150

200

250

Acrolein PubMed Citations

Current Research

Oral, inhalation exposure Physiologic efects

Acute lung injury, COPD Multiple sclerosis, myelin damage Alzheimer’s disease Cardiomyopathy

Current Research

In vitro Oxidative stress Apoptosis DNA adduction Inflammation Mutagenicity

Special Issue on AcroleinSeptember 2011

Future

Tremendous potential to explore hypotheses and prioritize risk

NATA 2005 177 air toxics and diesel particulate matter

NHIS 2000 — 2009 Great variety of health outcomes

Merges with other data Medicare enrollment and claims National Death Index Social Security benefits

B. Rey de Castro, Sc.D.Centers for Disease Control

National Center for Environmental HealthAtlanta, Georgia

rdecastro@cdc.gov+1 770 488 0162

www.slideshare.net

National Center for Health Statistics

Office of Analysis & Epidemiology, Special Projects Branch