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Health Effects of Air Pollution: Asthma and Cardiovascular Outcomes

Health Effects of Air Pollution: Asthma and Cardiovascular Outcomes. Ralph J. Delfino, MD, PhD Epidemiology Division, Dept. Medicine, & Genetic Epidemiology Research Institute University of California, Irvine. Asthma Phenotype.

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Health Effects of Air Pollution: Asthma and Cardiovascular Outcomes

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  1. Health Effects of Air Pollution: Asthma and Cardiovascular Outcomes Ralph J. Delfino, MD, PhD Epidemiology Division, Dept. Medicine, & Genetic Epidemiology Research Institute University of California, Irvine

  2. Asthma Phenotype • Intermittent and reversible airway obstruction (usually measured with FEV1); • Airway hyperresponsiveness to contractile stimuli; • Airway inflammation: infiltration of inflammatory cells releasing cytokines, chemokines & chemical mediators. • increasingly measured with exhaled NO (eNO) • Allergic and non-allergic asthma

  3. Acute asthma outcomes linked to air pollution Experimental studies: • Increased bronchial hyperresponsiveness; Experimental and Epidemiological studies: • Decreased lung function; • Increased airway inflammation; • Increased allergic responses; • Increased asthma symptoms & as-needed medication use; Epidemiological studies: • Increased asthma morbidity from respiratory infections; • Hospital admissions and ED visits.

  4. Experimental Data on Polycyclic Aromatic Hydrocarbons (PAH) / DEP • PAH and other components from fossil fuel combustion (e.g., diesel exhaust particles) may contribute to: • worsening respiratory allergic responses (enhanced specific IgE & cytokine responses to allergen challenge) • induction of the initial clinical expression of atopy (allergic sensitization to neoantigens)

  5. Evidence from the Air Pollution Epidemiology Literature • Ambient Air Pollution • Time series studies (acute severe asthma morbidity requiring medical staff intervention) • Ambient, Outdoor Home and Personal Air Pollution • Panel studies (acute asthma outcomes) • Cohort studies (asthma onset)

  6. Time series analyses of asthma hospital admissions and ED Visits Significant associations between ozone and admissions or ED visits for asthma found in: • Southern Ontario, CanadaEnviron Res. 1987;43:317-31;Environ Res 1994;65:271-90 • AtlantaEnviron Res 1994;65:56-68; Am J Epidemiol 2000;151:798-810; JAMA 2001;285:897-905; Epidemiology2005;16: 164–174. • Seattle, WAEpidemiology 1999;10:23-30. • Brisbane and Melbourne AustraliaArch Environ Health 2001;56:37-52; Int J Environ Health Res 2005;15:11-20 • Madrid, SpainEur Respir J 2003;22:802-8 • Paris, FrancePediatr Pulmonol 2000;30:41-6 • Mexico CityAm J Epidemiol 1995;141:546-53 • Saint John, New Brunswick, CanadaEnviron Health Perspect 104:1354-60

  7. Optimal design to study acute effects on asthma in natural settings • Panel study:a longitudinal study with repeated measurements of health outcomes and exposures in individuals. • e.g., UCI Asthma Panel studies:Daily follow-up of children with persistent asthmain urban regions of Southern California with high levels of air pollution, primarily from mobile sources of fossil fuel combustion products.

  8. Panel Studies of Acute Asthma, Particulate Air Pollution & NO2(personal and ambient air pollutant exposures) • Asthma symptoms: episodes of interference with daily activity. • Lung Function: Forced expiratory volume in 1 sec (FEV1). • Airway inflammation: as represented by daily exhaled NO (eNO). • Markers of traffic-related air pollution: PM elemental carbon (EC), PM organic carbon (OC), and NO2

  9. Personal Exposure Monitors

  10. Percent Predicted FEV1 in Relation to Personal PM Alpine, CA Asthma Panel Study. Delfino et al. Environ Health Perspect 2004;112:932-41

  11. Percent Predicted FEV1 in Relation to PM2.5 mass

  12. Riverside and Whittier, CA Asthma Panel Study

  13. Riverside and Whittier, CA Asthma Panel Study

  14. Relationship of asthma symptoms to lag 0 PM10 and elemental and organic carbon fractions of PM10 Huntington Park, CA Asthma Panel Study. Delfino et al. Environ Health Perspect 2003; 111:647-656.

  15. Delfino et al. Environ Health Perspect, 2006;114:1736-43

  16. Riverside and Whittier, CA Asthma Panel Study

  17. Riverside and Whittier, CA Asthma Panel Study

  18. Riverside and Whittier, CA Asthma Panel Study

  19. ConclusionseNO and FEV1 are associated with personal PM2.5 independent of other pollutants, possibly due to more vs. less volatile components, and bioaerosol components (e.g., endotoxin);Air pollutant associations may be missed using ambient PM mass concentrations alone because the EC and OC PM fraction, or NO2, were more strongly associated with asthma symptoms, eNO and FEV1;Associations of eNO with ambient & personal EC and NO2 suggests traffic-related emission components are causally related to airway inflammation. Products of fossil fuel combustion Bioaerosols

  20. Traffic-related Air Pollution and Asthma Onset • Numerous epidemiologic studies have shown associations between traffic near the home and asthma prevalence or morbidity, and atopy. Reviewed in: • Delfino RJ. Environ Health Perspect, 2002; 110(Suppl 4):573-89. • Heinrich and Wichmann. Curr Opin Allergy Clin Immunol, 2004;4:341-8 • Sarnat and Holguin 2007 Curr Opin Pulm Med 2007;13:63-6 • These studies provide evidence that air pollution from primary emission sources is a risk factor for the development of asthma.

  21. Prevalence of asthma and black carbon at neighborhood schools, East Bay Children’s Respiratory Health Study Kim et al.Am J Respir Crit Care Med 170:520–526, 2004

  22. Prevalence of asthma in 1,330 children ages 5-7 yr by distance of residence to a major road in long-term residents, no family history of asthma. McConnell et al.Environ Health Perspect 2006;114:766–772

  23. Cardiovascular Health and Air Pollution • Morbidity and mortality time series:ambient air pollutant data and cause of admission or death. • Cohort studies:ambient air pollutant data and disease onset or cause of death. • Panel studies:ambient, home and personal air pollutant data and acute physiological or biological outcomes.

  24. Time Series Studies: MortalityDominici et al, 2003 • National Morbidity, Mortality and Air Pollution study (NMMAPS) 90 U.S. cities • 0.34% increase cardiorespiratory mortality (95% CI: 0.1, 0.57) per 10 g/m3 PM10 • largely independent of NO2, SO2 and O3

  25. Time Series Studies: Morbidity • Associations of ambient PM mass concentrations with cardiovascular hospital admissions found in numerous studies. • 14 U.S. cities (Janssen et al. 2002): PM10 from mobile source emissions and from oil combustion (EPA estimates) showed the strongest associations with cardiovascular admissions vs. fugitive dust, wood burning, coal.

  26. Cohort Studies: Pope et al. 2004 Circulation 109:71-77 • Up to 500,000 persons in the American Cancer Society study, with 16 years follow-up across U.S. urban areas. • 10 g/m3 increase in PM2.5 was associated with 8-18% increases in mortality due to ischemic heart disease, dysrhythmias, heart failure, and cardiac arrest.

  27. Cohort Studies: Hoek et al. 2002Lancet 360:1203-09 • 5,000 persons with 8 years follow-up in the Netherlands Cohort Study on Diet and Cancer. • Cardiopulmonary mortality was more strongly associated with: • living near high traffic density (100 m to freeway or 50 m to major urban road) RR 1.95 (95% CI: 1.09, 3.52) vs. • Est. ambient background black smoke:RR 1.34 (0.68-2.64)

  28. Questions regarding cardiovascular M&M associations with air pollution • Causal pollutant components and sources? • Biological mechanisms? • Airwayinflammation,oxidative stress, and activation of leukocytes  systemic effects; • Autonomic dysfunction (decreased HRV, arrhythmias); • Systemic oxidative stress & inflammation & platelet activation / coagulation / thrombosis; (coronary artery obstruction, stroke) • Endothelial dysfunction (with increased blood pressure and above)

  29. ROS & RNS from PM  acute systemic inflammation, oxidative stress, platelet and endothelial cell activation, platelet-leukocyte adhesion and leukocyte transmigration  atherosclerotic plaque instability and rupture. Chronically– atherosclerosis. PM-induced myocardial infarction Adherence andentry of white blood cells Vascular smooth muscle cell migration Adherence andaggregation of platelets Foam-cellformation Inflammatory cell activation

  30. Cardiovascular Health and Air Pollution Study (CHAPS)air monitoring trailer and mobile biospecimen lab Funding: NIH, CARB & AQMD, EPA So. Cal. Particle Center

  31. Causal pollutant components & sources? • Problems with ambient exposure data: • Exposure error: data often measured at great distance from subjects; • Reliance on PM2.5 or PM10 mass alone: components & size distributions vary over space & time. • Solutions in CHAPS are to measure: • Microenvironmental PM exposures (indoor exposure to PM of outdoor origin); • Size-fractionated PM & particle no. conc; • PM sources & components using tracer methods (SOA and primary OC) & surrogates (e.g., EC).

  32. Hypotheses • Biomarkers of inflammation, thrombosis and oxidative stress/antioxidant activity in subjects with CAD will be associated with outdoor home PM mass and number concentration. • These associations will be supported and clarified by models based on: • indoor PM exposures of outdoor origin, • ultrafine vs. larger size fractions, and • exposure markers of traffic-related primary or secondary PM sources and components.

  33. Population and Design (year 1 of 2) • 30 nonsmoking subjects age  65 yr, confirmed diagnosis of coronary artery disease; • Two Retirement Communities (independent living) in east and west San Gabriel Valley; • 12 weekly repeated blood draws for biomarkers in each subject.

  34. Conclusions • Positive associations of biomarkers of systemic inflammation with PM are largely driven by markers of primary combustion sources (EC, BC, primary OC); • Outdoor PM associations are supported by associations for indoor exposures to PM of outdoor origin; • PN and quasi-ultrafine conc. are more strongly associated with biomarkers than accumulation mode PM & SOA supporting hypotheses regarding UFP (translocation?);

  35. Conclusions • Inverse associations of biomarkers of antioxidant activity (SOD and GPx) with PM are also largely driven by markers of primary combustion sources (EC, BC, primary OC); • Inactivation of antioxidant enzymes (SOD, GPx-1) by ROS, RNS or electrophiles may be one mechanism of pollutant-induced systemic inflammation and thrombosis. • These findings are consistent with the view that oxidative stress and inflammation may underlie the morbidity and mortality findings.

  36. Thank-you

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