Acrolein is an air toxic with high potency as a respiratory irritant. There is strikingly little epidemiology available for acrolein although US EPA estimates that acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 National-Scale Air Toxics Assessment (NATA). We addressed this data gap by geographically linking 2005 NATA acrolein exposure estimates at the census tract with residences of participants in the National Health Interview Survey (NHIS) for 2000-2009 (n = 216,371). The NHIS monitors the health of the civilian, non-institutionalized population of the United States through a comprehensive interview of a nationally representative sample of households. The health outcome was self-reported asthma attack in the previous 12 months among adults 18 years and older. In the highest quintile of acrolein exposure (>0.055 ug/m3), there was a borderline statistically significant increase in asthma attack prevalence (pOR [95% CI]= 1.11 [1.00:1.23]), controlling for smoking, sex, age, education, race, poverty, insurance, access to care, urban/rural residence, and survey year. Stratifying the analysis by urban and rural residence, exposure to the highest quintile of acrolein concentration in urban areas was borderline statistically significant (1.13 [1.00:1.29]), while in rural areas it was not (1.08 [0.80:1.44]).

1. 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, MD
October 24, 2011
National Center for Health Statistics
Office of Analysis & Epidemiology, Special Projects Branch

2. Acrolein
 Aldehyde
 Hazardous Air Pollutant subject to Clean Air Act

3. Ubiquitous
 Combustion
 Tobacco
 Mobile sources, especially diesel
 Airports
 Wood heating & forest fires
 Industrial boilers
 Indoor air pollutant
 Cooking
 Smoking

4. 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.

5. 2005 TRI: Acrolein

6. Exposure
 Inhalation
 Combustion by-products
 Cigarette smoke
 Cooking smoke
 Food
 Heating carbohydrates, lipids, certain amino acids
 Formed physiologically
 Oxidative stress
 Polyamine metabolism

7. Highly Potent Irritant
 Acute and chronic (non-cancer) effects
 Respiratory congestion
 Eye, nose, throat
 Skin
 Especially sensitive
 Asthmatics
 Allergy sufferers

8. Regulatory Ambient Exposure Levels
LC50 750
1000
100
Log10 Ambient Acrolein Concentration [mg/m3]
NIOSH IDLH
10 4.6
LOAEL NIOSH STEL
0.9 0.8 OSHA PEL ACGIH Ceiling
1 NIOSH REL EPA AEGL2 8h
0.25 0.23
EPA AEGL1 8h
0.1 0.07
0.01
0.001
0.0001
RfC 0.00002
0.00001
1 2 3 4 5 6 7 8

9. 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

10. 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

11. Therefore,
no epidemiologic
research on acrolein

12. 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

13. 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

16. NATA 2005
 EPA says:
 Acrolein responsible for ―about 75 percent of the nationwide
average non-cancer hazard‖
 Remarkable for air toxic with no epidemiology

17. Now that we have
exposure estimates,
what if we could get
health effects data?

18. 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

19. National Health Interview Survey
 Interview
 Face to face
 Computer-aided
 Data
 N ~ 40,000 households (~87,000 individuals) annually
 Initiated in 1957

20. Multistage Population Sampling

21. Complex Survey Design
 Cross-sectional
 Use of weighting, clustering, and stratification
 Oversampling
 Variance estimation complicated
 Special software: SUDAAN™
 Taylor series linearization method (GEE)

22. 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

23. 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

24. NATA-NHIS Data Merge
NATA: NHIS:
Acrolein Adult
Exposure Asthma
Merge by
Census
Tract
Merged
NATA-
NHIS Data

25. 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

26. 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

27. Population-Weighted Outdoor Acrolein Exposure
[µg/m3]
Mean (SE) 3.34E-2 (3.94E-4)
Geometric Mean (GSE) 2.27E-2 (2.43E-4)

28. Population-Weighted Outdoor Acrolein Exposure
[µg/m3]
Median (IQR) 2.45E-2 (3.11E-2)
5th Percentile 4.97E-3
10th 6.62E-3
25th 1.22E-2
75th 4.34E-2
90th 6.87E-2
95th 8.78E-2

29. 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

30. 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

31. Complex Survey Variance Estimation
 Taylor series linearization (GEE)
 Survey sample weights 2000 — 2009
 Indicators for survey stratum and PSU

32. pOR by Acrolein Quintile
1.30
1.20
1.10
pOR
1.00
0.90
0.80
1 2 3 4 5
Exposure Quintile

33. 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

34. 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

35. Confounders
 Statistically significant
 Race, sex, age, smoking, education, access to
healthcare, urban/rural residence, survey year
 Not statistically significant
 Insurance coverage, survey quarter

36. Strengths
 Inexpensive data collection and design
 Large sample
 National geographic coverage
 Census tract resolution
 Generalizable to US population
38

37. Limitations
 Uncertainty of NATA exposure estimates
 Merge bias
 Cross-sectional
 Acrolein from indoor air, food
 Effect estimation in smaller areas severely limited
39

38. Feasible to conduct
national epidemiologic
analysis with modeled
chronic exposure estimates
for air toxics

39. First demonstration of
acrolein’s adverse effect
on general population

40. Approaches to Acrolein Exposure Assessment
Modeled
Exposure
Assessment
Measurement Biomarkers

41. 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

42. Acrolein PubMed Citations
250
200
150
100
50
0
2005 2006 2007 2008 2009 2010 2011 to
October 19

43. Current Research
 Oral, inhalation exposure
 Physiologic efects
 Acute lung injury, COPD
 Multiple sclerosis, myelin damage
 Alzheimer’s disease
 Cardiomyopathy

44. Current Research
 In vitro
 Oxidative stress
 Apoptosis
 DNA adduction
 Inflammation
 Mutagenicity

45. Special Issue on Acrolein
September 2011

46. 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

47. B. Rey de Castro, Sc.D.
Centers for Disease Control
National Center for Environmental Health
Atlanta, Georgia
rdecastro@cdc.gov
+1 770 488 0162
www.slideshare.net
National Center for Health Statistics
Office of Analysis & Epidemiology, Special Projects Branch