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    PPT PPT Presentation Transcript

    • Health Effects of Air Pollution March 17, 2010 Presented by David B. Peden, M.D., M.S. Professor of Pediatrics, Medicine & Microbiology/Immunology Director, UNC Center for Environmental Medicine, Asthma and Lung Biology
    • Disclosures
      • CORPORATE
      • GlaxoSmithKline
      • Funxional Therapeutics
      • FEDERAL
      • US EPA
      • NHLBI
      • NIEHS
      • NCCAM
    • Sources of Common Environmental Contaminants Which Modify Asthma
    • National Ambient Air Quality Standards (NAAQS) Pollutant Primary Stds. Averaging Times Carbon Monoxide 9 ppm (10 mg/m 3 ) 8-hour (1) 35 ppm (40 mg/m 3 ) 1-hour (1) Lead 1.5 µg/m 3 Quarterly Average Nitrogen Dioxide 0.053 ppm (100 µg/m 3 ) Annual (Arithmetic Mean) Particulate Matter (PM 10 ) Revoked (2) Annual (2) (Arith. Mean) 150 µg/m 3 24-hour (3) Particulate Matter (PM 2.5 ) 15.0 µg/m 3 Annual (4) (Arith. Mean) 35 µg/m 3 24-hour (5) Ozone 0.075 ppm 8-hour (6) 0.12 ppm 1-hour (7) (Applies only in limited areas) Sulfur Oxides 0.03 ppm Annual (Arith. Mean) 0.14 ppm 24-hour (1)
    • Pollutants and Asthma
    • Environmental Agents Which Induce Asthma, Allergies and Lung Disease
      • Probable
        • Diesel Exhaust
        • ETS
      • Possible
        • O 3
        • NO 2
        • Other Particulates
      • Plausible
        • Low dose endotoxin
      (Gauderman et al NEJM, 2004, 351:1057-1067)
    • Environmental Agents Which Worsen Asthma and Allergies
      • Ozone
      • SO 2
      • NO 2
      • Diesel Exhaust
      • Particulates
      • Environmental Tobacco Smoke
      • Endotoxin
      Burnett, RT et al. Am J Epidemiol. 2001 Mar 1;153(5):444-52
    • Impact of steel mill closing on PM 2.5 (left,  g/m 3 ) and Bronchitis admissions (right) in the Utah Valley (Pope, et al) 0 10 20 30 40 50 60 70 80 1985 1986 1987 1988 Steel Mill Closed 0 25 50 75 100 125 150 1985 1986 1987 1988 Steel Mill Closed
    • Endotoxin exposure is a risk factor for asthma: the national survey of endotoxin in United States housing. Am J Respir Crit Care Med. 2005 Dec 1;172(11):1371-7
    • Pollutants shown to enhance recall response to allergen
      • Ozone
      • NO 2 /SO 2
      • Endotoxin
      • Diesel Exhaust
      • ETS
      • Responses include:
        • IgE
        • PMNs
        • Eosinophils
        • Airway Reactivity
    • Airway Responses of Asthmatics to Ozone
    • Copyright restrictions may apply. Daily Levels of Ozone (Both 1-Hour Average and 8-Hour Average), Particulate Matter of 2.5 {micro}m or Less (PM2.5), and Daily Maximum Temperature, With Daily Prevalence of Respiratory Symptoms for Users of Asthma Maintenance Medication (n = 130) for Southern New England, April 1 through September 30, 2001 Gent, J. F. et al. JAMA 2003;290:1859-1867
    • Granulocyte Response to O 3
    • Effect of O 3 on IL-1  and IL-6 in Asthma and Normal Volunteers
    • Effect of O 3 on IL-8 and IL-10 in Asthma and Normal Volunteers
    • Ozone Enhances Markers of Innate Immunity and Antigen Presentation on Airway Monocytes in Healthy Individuals J Allergy Clin Immunol. 2007 Sep;120(3):719-22
    • Ozone enhances response to inhaled allergens
      • Ozone exposure causes increased immediate allergic responses to house dust mite
      • Ozone causes increased eosinophil (allergy cell) influx to the airway
      • Experimentally demonstrated at levels as low as 0.12 ppm
    • Summary
      • Epidemiological Studies clearly demonstrate an effect of ambient air ozone in asthma
      • Ozone causes an immediate decrease in lung function
      • Ozone induced airway inflammation
        • PMNs in all populations
        • Eosinophils-seen in asthmatics
      • Ozone results in changes in airway cell surface markers which likely modulate immune response
      • Ozone increases response to allergen
    • Climate Change, Pollutants and Environmental Allergens
    • Global temperature land-ocean anomaly (°C), 1880-2007, defined as the difference from the average temperature of the base period (1951-1980). The 14 warmest years in the global temperature record have all occurred since 1990. The blue points (annual means) in the box from 1990-2007 show the warmest years. Adapted from: NASA 2007
    • Predicted increase in ambient O 3 by 2050 resulting from Climate Change Bell et al, Climatic Change (2007) 82:61–76 DOI 10.1007/s10584-006-9166-7
    • Predicted exceedance of the 1 and 8 hour O 3 standard by 2050 resulting from Climate Change Bell et al, Climatic Change (2007) 82:61–76 DOI 10.1007/s10584-006-9166-7
    • Singer BD, Ziska LH, Frenz DA, Gebhard DE, Straka JG (2005) Increasing Amb a 1 content in common ragweed (Ambrosia artemisiifolia) pollen as a function of rising atmospheric CO2 concentration. Functional Plant Biology 32, 667–670. Increased CO 2 linked to increased Ragweed Pollen and increased Amb a 1 concentration/mg pollen
    • Effect of Urbanization on Ragweed growth Ziska LH et al JACI, 2003
    • Oxidant Stress and Pollutants A unifying concept for the impact of pollutants in asthma
    • Oxidant stress is a common theme in the action of a wide variety of air pollutants in inflammatory processes.
      • Pollutants & oxidant stress:
        • Pollutants themselves
          • O 3 , metals
        • Products from pollutants
          • Polyaromatic hydrocarbons & quinones from DEP and ETS
        • Oxidants from macrophages and granulocytes
          • Singlet oxygen, H 2 O 2 , superoxide
      Cross, CE et al, American Journal of Respiratory and Critical Care Medicine Vol 166. pp. S44-S50, (2002)
    • GSTM1 polymorphisms and and lung disease in humans ETS, DEP and O 3
    • GSTM1
      • NRF2 nuclear transcription factor
      • GSTM1 Null
        • Associated with increased response to ozone
        • Associated with increased response to diesel exhaust
        • Associated with increased response to tobacco smoke
    • Effect of GSTM1 null genotype on asthma relative to tobacco smoke exposure
      • Effect of maternal smoking during pregnancy on asthma in GSTM1- children (panel to the left, Gilliland et al, AJRCCM 166:457-463, 2002)
      • GSTM1- children exposed to environmental tobacco smoke have a 5.5 odds ratio risk of current asthma relative to GSTM+ children (Kabesch et al, Thorax 59:569 2004)
    • DEP effect on the response to allergen stratified by GSTM1 genotype Gilliland et al, Lancet. 2004 Jan 10;363(9403):119-25
      • Following DEP challenge, GSTM1 null individuals (vs. GSTM1+) have increased:
        • allergen-induced IgE (right)
        • histamine (not shown)
    • Effect of GSTM1 genotype and ozone induced decreases in FEF25-75 in asthmatics Romieu et al, Thorax 2004;59:8-10
      • GSTM1 null asthmatics have increased asthma symptoms with ozone exposure than do GSTM1 sufficient persons
    • Effect of the GSTM1 null genotype on lung function and inflammatory response to 0.4 ppm ozone Alexis et al, JACI 2009, available on line
    • Effect of the GSTM1 null genotype on airway cell function, IL-1  & IL-8 post ozone challenge GSTM1 did impact cell function but not IL-1  or IL-8 Alexis et al, JACI 2009, available on line
    • GSTM1 and ozone summary
      • GSTM1 does not determine lung function repsonse to ozone
      • GSTM1 null has a delayed PMN response to ozone
      • GSTM1 null vs.sufficient have different cell marker changes in airway monocytes
    • What to do about pollutant-induced disease Patient and societal interventions
    • Pollutant Avoidance
      • Decrease tobacco use
      • Local Environmental Control
      • Live away from a roadway
      • Societal Changes (decrease traffic, better fuels)
    • Changes in Traffic Patterns 1996 Atlanta Olympics
    • Copyright restrictions may apply. Friedman, M. S. et al. JAMA 2001;285:897-905. Mean Levels of Major Pollutants Before, During, and After the 1996 Summer Olympic Games as a Percentage of the National Ambient Air Quality Standard (NAAQS)
    • Friedman, M. S. et al. JAMA 2001;285:897-905.
    • Inhaled Steroids Effect on response to pollutants
    • Inhaled Corticosteroids and Endotoxin
      • Inhaled corticosteroids
        • Decreases baseline eosinophilic inflammation
        • Decreases CD14 expression on airway monocytes and macrophages
        • Decreases PMN influx to inhaled endotoxin
    • Antioxidants and Asthma Treatment Is this an option?
    • Vitamin E + C supplementation protects asthmatics from O 3 -induced changes in lung function and inflammation children with allergic asthma
      • Combination ascorbate and alpha tocopherol:
        • Decrease effect of ambient O 3 exposure on FEF25-75 and PEFR
        • Decrease O 3 related inflammation
      • Other reports:
        • Combination therapy decreased lung function response to O 3 challenge in normal volunteers and asthmatics
        • Ascorbate may protect against exercise-induced asthma
      Romieu et al, AJRCCM Vol 166. pp. 703-709, (2002) Sienra-Monge et al, Clin & Exp Immunology 138 (2), 317-322. (2004)
    • Acknowledgements
      • Neil Alexis
      • Philip Bromberg
      • John Lay
      • Haibo Zhou
      • Michelle Hernandez
      • Carole Robinette
      • Martha Almond
      • Peg Herbst
      • Aline Kala
      • Lynne Newlin-Clapp
      • Sally Ivins
      • Heather Wells
      • Nolan Sweeney
      • Madeline Dillon
      • Jessica Wiser
      • Marlowe Eldridge
      • Robert Roubey
      • Dhaval Pate l
      • Robert Devlin
      • David Diaz-Sanchez
      • Howard Kehrl
      • Martin Case
      • Steven Kleeberger