Скачать презентацию Health Effects of Air Pollution March 17 2010 Скачать презентацию Health Effects of Air Pollution March 17 2010

24ecf5eaf1be550ac8284b15d6ac6bfd.ppt

  • Количество слайдов: 45

Health Effects of Air Pollution March 17, 2010 Presented by David B. Peden, M. 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 • Glaxo. Smith. Kline • Funxional Therapeutics • • • FEDERAL Disclosures • CORPORATE • Glaxo. Smith. Kline • Funxional Therapeutics • • • FEDERAL US EPA NHLBI NIEHS NCCAM 2

Sources of Common Environmental Contaminants Which Modify Asthma Sources of Common Environmental Contaminants Which Modify Asthma

National Ambient Air Quality Standards (NAAQS) Pollutant Primary Stds. Averaging Times Carbon Monoxide 9 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) 15. 0 µg/m 3 Annual(4) (Arith. Mean) 35 µg/m 3 24 -hour(5) 0. 075 ppm 8 -hour(6) 0. 12 ppm 1 -hour(7)(Applies only in limited areas) 0. 03 ppm Annual (Arith. Mean) 0. 14 ppm 24 -hour(1) Particulate Matter (PM 2. 5) Ozone Sulfur Oxides

Pollutants and Asthma Pollutants and Asthma

Environmental Agents Which Induce Asthma, Allergies and Lung Disease • Probable » Diesel Exhaust 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 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, mg/m 3) and Bronchitis Impact of steel mill closing on PM 2. 5 (left, mg/m 3) and Bronchitis admissions (right) in the Utah Valley (Pope, et al) 80 150 70 125 Steel Mill Closed 60 100 50 75 40 30 50 20 25 10 0 0 1985 1986 1987 1988

Endotoxin exposure is a risk factor for asthma: the national survey of endotoxin in 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 9

Pollutants shown to enhance recall response to allergen • • • Ozone NO 2/SO Pollutants shown to enhance recall response to allergen • • • Ozone NO 2/SO 2 Endotoxin Diesel Exhaust ETS Responses include: » » Ig. E PMNs Eosinophils Airway Reactivity 10

Airway Responses of Asthmatics to Ozone Airway Responses of Asthmatics to Ozone

Daily Levels of Ozone (Both 1 -Hour Average and 8 -Hour Average), Particulate Matter Daily Levels of Ozone (Both 1 -Hour Average and 8 -Hour Average), Particulate Matter of 2. 5 {micro}m or Less (PM 2. 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 Copyright restrictions may apply.

Granulocyte Response to O 3 Granulocyte Response to O 3

Effect of O 3 on IL-1 b and IL-6 in Asthma and Normal Volunteers Effect of O 3 on IL-1 b and IL-6 in Asthma and Normal Volunteers

Effect of O 3 on IL-8 and IL-10 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 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 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 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 Climate Change, Pollutants and Environmental Allergens

Global temperature land-ocean anomaly (°C), 1880 -2007, defined as the difference from the average 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 20

Predicted increase in ambient O 3 by 2050 resulting from Climate Change Bell et Predicted increase in ambient O 3 by 2050 resulting from Climate Change Bell et al, Climatic Change (2007) 82: 61– 76 DOI 10. 1007/s 10584 -006 -9166 -7 21

Predicted exceedance of the 1 and 8 hour O 3 standard by 2050 resulting 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/s 10584 -006 -9166 -7 22

Singer BD, Ziska LH, Frenz DA, Gebhard DE, Straka JG (2005) Increasing Amb a 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 CO 2 concentration. Functional Plant Biology 32, 667– 670. Increased CO 2 linked to increased Ragweed Pollen and increased Amb a 1 concentration/mg pollen 23

Effect of Urbanization on Ragweed growth Ziska LH et al JACI, 2003 24 Effect of Urbanization on Ragweed growth Ziska LH et al JACI, 2003 24

Oxidant Stress and Pollutants A unifying concept for the impact of pollutants in asthma 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 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. S 44 -S 50, (2002)

GSTM 1 polymorphisms and lung disease in humans ETS, DEP and O 3 GSTM 1 polymorphisms and lung disease in humans ETS, DEP and O 3

GSTM 1 • NRF 2 nuclear transcription factor • GSTM 1 Null » Associated GSTM 1 • NRF 2 nuclear transcription factor • GSTM 1 Null » Associated with increased response to ozone » Associated with increased response to diesel exhaust » Associated with increased response to tobacco smoke

Effect of GSTM 1 null genotype on asthma relative to tobacco smoke exposure • Effect of GSTM 1 null genotype on asthma relative to tobacco smoke exposure • Effect of maternal smoking during pregnancy on asthma in GSTM 1 - children (panel to the left, Gilliland et al, AJRCCM 166: 457 -463, 2002) • GSTM 1 - 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 GSTM 1 genotype Gilliland et DEP effect on the response to allergen stratified by GSTM 1 genotype Gilliland et al, Lancet. 2004 Jan 10; 363(9403): 119 -25 • Following DEP challenge, GSTM 1 null individuals (vs. GSTM 1+) have increased: » allergen-induced Ig. E (right) » histamine (not shown)

Effect of GSTM 1 genotype and ozone induced decreases in FEF 25 -75 in Effect of GSTM 1 genotype and ozone induced decreases in FEF 25 -75 in asthmatics Romieu et al, Thorax 2004; 59: 8 -10 • GSTM 1 null asthmatics have increased asthma symptoms with ozone exposure than do GSTM 1 sufficient persons

Effect of the GSTM 1 null genotype on lung function and inflammatory response to Effect of the GSTM 1 null genotype on lung function and inflammatory response to 0. 4 ppm ozone Alexis et al, JACI 2009, available on line 32

Effect of the GSTM 1 null genotype on airway cell function, IL-1 b & Effect of the GSTM 1 null genotype on airway cell function, IL-1 b & IL-8 post ozone challenge GSTM 1 did impact cell function but not IL-1 b or IL-8 Alexis et al, JACI 2009, available on line 33

GSTM 1 and ozone summary • GSTM 1 does not determine lung function repsonse GSTM 1 and ozone summary • GSTM 1 does not determine lung function repsonse to ozone • GSTM 1 null has a delayed PMN response to ozone • GSTM 1 null vs. sufficient have different cell marker changes in airway monocytes

What to do about pollutantinduced disease Patient and societal interventions What to do about pollutantinduced disease Patient and societal interventions

Pollutant Avoidance • • Decrease tobacco use Local Environmental Control Live away from a 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 Changes in Traffic Patterns 1996 Atlanta Olympics

Mean Levels of Major Pollutants Before, During, and After the 1996 Summer Olympic Games 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. Copyright restrictions may apply.

Friedman, M. S. et al. JAMA 2001; 285: 897 -905. Friedman, M. S. et al. JAMA 2001; 285: 897 -905.

Inhaled Steroids Effect on response to pollutants Inhaled Steroids Effect on response to pollutants

Inhaled Corticosteroids and Endotoxin • Inhaled corticosteroids » Decreases baseline eosinophilic inflammation » Decreases Inhaled Corticosteroids and Endotoxin • Inhaled corticosteroids » Decreases baseline eosinophilic inflammation » Decreases CD 14 expression on airway monocytes and macrophages » Decreases PMN influx to inhaled endotoxin

42 42

Antioxidants and Asthma Treatment Is this an option? Antioxidants and Asthma Treatment Is this an option?

Vitamin E + C supplementation protects asthmatics from O 3 induced changes in lung 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 FEF 25 -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) 44

Acknowledgements • • • • Neil Alexis Philip Bromberg John Lay Haibo Zhou Michelle 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 Patel Robert Devlin David Diaz. Sanchez • Howard Kehrl • Martin Case • Steven Kleeberger 45