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Acrolein and Adult Asthma in a NationallyRepresentative Sample of the United States                         B. Rey de Cast...
Acrolein   Aldehyde   Hazardous Air Pollutant subject to Clean Air Act
Ubiquitous   Combustion       Tobacco       Mobile sources, especially diesel       Airports       Wood heating & for...
Ubiquitous   Largest industrial uses     Synthesis of acrylic acid     Biocide   Two biggest emitting facilities in Al...
2005 TRI: Acrolein
Exposure   Inhalation     Combustion by-products     Cigarette smoke     Cooking smoke   Food     Heating carbohydra...
Highly Potent Irritant   Acute and chronic (non-cancer) effects   Respiratory congestion   Eye, nose, throat   Skin  ...
Regulatory Ambient Exposure Levels                                                         LC50 750                       ...
Ambient Measurement Very Difficult   Highly reactive   Ambient formation     Even within samplers   Sensitive to     ...
Current Ambient Methods   US EPA       TO-11a: canister sampler       TO-15: cartridge sampler       TO-15 superseding...
Therefore, no epidemiologicresearch on acrolein
Alternative 1: Exposure Biomarkers   Urine   Mercapturic acid metabolites   Analytical methods recently developed at CD...
Alternative 2: Modeled Exposure   US EPA National-Scale Air Toxics Assessment 2005   Nationwide estimate of chronic inha...
NATA 2005   EPA says:     Acrolein responsible for ―about 75 percent of the nationwide      average non-cancer hazard‖ ...
Now that we haveexposure estimates,what if we could gethealth effects data?
Nationwide Health Effects   National Health Interview Survey 2000 — 2009   Content     Health conditions and behaviors ...
National Health Interview Survey   Interview     Face to face     Computer-aided   Data     N ~ 40,000 households (~8...
Multistage Population Sampling
Complex Survey Design   Cross-sectional   Use of weighting, clustering, and stratification   Oversampling   Variance e...
NHIS 2000 — 2009   10 years NHIS data   Adults 18 years-old and over   Self-reported asthma attack in previous 12 month...
NHIS Confidential Data   Aim: geographic merge with NATA 2005   Data not for public use     Geocoded NHIS subject resid...
NATA-NHIS Data Merge NATA:                             NHIS:Acrolein                           AdultExposure              ...
NATA 2005 & NHIS 2000-2009   Sample size: 209, 365 subjects     72.8 percent of 287,530 subjects   Census tracts: 14,93...
NATA 2005 & NHIS 2000—2009   White: 71.5 percent   Male: 48.8 percent   Age: ≥18 years-old   Never smokers: 55.5 perce...
Population-Weighted Outdoor Acrolein Exposure                         [µg/m3]    Mean (SE)            3.34E-2 (3.94E-4)   ...
Population-Weighted Outdoor Acrolein Exposure                         [µg/m3]        Median (IQR)     2.45E-2 (3.11E-2)   ...
Logistic Regression Model   Binary outcome: asthma attack last 12 months     NHIS 2000 — 2009     Self-report   Predic...
Potential Asthma Confounders   Race, sex, age, smoking, education, insurance    coverage, access to healthcare, urban/rur...
Complex Survey Variance Estimation   Taylor series linearization (GEE)   Survey sample weights 2000 — 2009   Indicators...
pOR by Acrolein Quintile      1.30      1.20      1.10pOR      1.00      0.90      0.80             1        2        3   ...
Primary Result   At highest quintile of acrolein exposure     0.0551 – 0.457 µg/m3     pOR 1.11 [1.00:1.23] adult asthm...
Stratified Analysis by Residence   Urban at highest quintile of acrolein exposure     pOR 1.13 [1.00:1.29] adult asthma...
Confounders   Statistically significant     Race, sex, age, smoking, education, access to      healthcare, urban/rural r...
Strengths        Inexpensive data collection and design        Large sample        National geographic coverage       ...
Limitations        Uncertainty of NATA exposure estimates        Merge bias        Cross-sectional        Acrolein fro...
Feasible to conduct  national epidemiologic  analysis with modeledchronic exposure estimates        for air toxics
First demonstration ofacrolein’s adverse effect on general population
Approaches to Acrolein Exposure Assessment                Modeled                Exposure               Assessment   Measu...
Acknowledgements   Jenifer Parker, Ph.D.     Chief, NCHS OAE Special Projects Branch     Merged EPA air quality data wi...
Acrolein PubMed Citations250200150100 50  0      2005   2006     2007      2008      2009   2010    2011 to               ...
Current Research   Oral, inhalation exposure   Physiologic efects       Acute lung injury, COPD       Multiple scleros...
Current Research   In vitro       Oxidative stress       Apoptosis       DNA adduction       Inflammation       Muta...
Special Issue on Acrolein   September 2011
Future   Tremendous potential to explore hypotheses and    prioritize risk   NATA 2005     177 air toxics and diesel pa...
B. Rey de Castro, Sc.D.      Centers for Disease ControlNational Center for Environmental Health             Atlanta, Geor...
Acrolein and Adult Asthma in a Nationally Representative Sample of the United States
Acrolein and Adult Asthma in a Nationally Representative Sample of the United States
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Acrolein and Adult Asthma in a Nationally Representative Sample of the United States

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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]).

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Acrolein and Adult Asthma in a Nationally Representative Sample of the United States

  1. 1. Acrolein and Adult Asthma in a NationallyRepresentative 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. 2. Acrolein Aldehyde Hazardous Air Pollutant subject to Clean Air Act
  3. 3. Ubiquitous Combustion  Tobacco  Mobile sources, especially diesel  Airports  Wood heating & forest fires  Industrial boilers Indoor air pollutant  Cooking  Smoking
  4. 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. 5. 2005 TRI: Acrolein
  6. 6. Exposure Inhalation  Combustion by-products  Cigarette smoke  Cooking smoke Food  Heating carbohydrates, lipids, certain amino acids Formed physiologically  Oxidative stress  Polyamine metabolism
  7. 7. Highly Potent Irritant Acute and chronic (non-cancer) effects Respiratory congestion Eye, nose, throat Skin Especially sensitive  Asthmatics  Allergy sufferers
  8. 8. Regulatory Ambient Exposure Levels LC50 750 1000 100Log10 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. 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. 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. 11. Therefore, no epidemiologicresearch on acrolein
  12. 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. 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
  14. 14. NATA 2005 EPA says:  Acrolein responsible for ―about 75 percent of the nationwide average non-cancer hazard‖ Remarkable for air toxic with no epidemiology
  15. 15. Now that we haveexposure estimates,what if we could gethealth effects data?
  16. 16. 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
  17. 17. National Health Interview Survey Interview  Face to face  Computer-aided Data  N ~ 40,000 households (~87,000 individuals) annually  Initiated in 1957
  18. 18. Multistage Population Sampling
  19. 19. Complex Survey Design Cross-sectional Use of weighting, clustering, and stratification Oversampling Variance estimation complicated  Special software: SUDAAN™  Taylor series linearization method (GEE)
  20. 20. 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
  21. 21. 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
  22. 22. NATA-NHIS Data Merge NATA: NHIS:Acrolein AdultExposure Asthma Merge by Census Tract Merged NATA- NHIS Data
  23. 23. 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
  24. 24. 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
  25. 25. Population-Weighted Outdoor Acrolein Exposure [µg/m3] Mean (SE) 3.34E-2 (3.94E-4) Geometric Mean (GSE) 2.27E-2 (2.43E-4)
  26. 26. 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
  27. 27. 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
  28. 28. 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
  29. 29. Complex Survey Variance Estimation Taylor series linearization (GEE) Survey sample weights 2000 — 2009 Indicators for survey stratum and PSU
  30. 30. pOR by Acrolein Quintile 1.30 1.20 1.10pOR 1.00 0.90 0.80 1 2 3 4 5 Exposure Quintile
  31. 31. 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
  32. 32. 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
  33. 33. Confounders Statistically significant  Race, sex, age, smoking, education, access to healthcare, urban/rural residence, survey year Not statistically significant  Insurance coverage, survey quarter
  34. 34. Strengths  Inexpensive data collection and design  Large sample  National geographic coverage  Census tract resolution  Generalizable to US population38
  35. 35. Limitations  Uncertainty of NATA exposure estimates  Merge bias  Cross-sectional  Acrolein from indoor air, food  Effect estimation in smaller areas severely limited39
  36. 36. Feasible to conduct national epidemiologic analysis with modeledchronic exposure estimates for air toxics
  37. 37. First demonstration ofacrolein’s adverse effect on general population
  38. 38. Approaches to Acrolein Exposure Assessment Modeled Exposure Assessment Measurement Biomarkers
  39. 39. 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
  40. 40. Acrolein PubMed Citations250200150100 50 0 2005 2006 2007 2008 2009 2010 2011 to October 19
  41. 41. Current Research Oral, inhalation exposure Physiologic efects  Acute lung injury, COPD  Multiple sclerosis, myelin damage  Alzheimer’s disease  Cardiomyopathy
  42. 42. Current Research In vitro  Oxidative stress  Apoptosis  DNA adduction  Inflammation  Mutagenicity
  43. 43. Special Issue on Acrolein September 2011
  44. 44. 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
  45. 45. B. Rey de Castro, Sc.D. Centers for Disease ControlNational 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

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