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Hasan Bayram, MD, PhD. Department of Chest Diseases, School of Medicine, University of Gaziantep

From Bench to Bedside; What Should a Physician Know About Air Pollution and How to Help the Patient. Hasan Bayram, MD, PhD. Department of Chest Diseases, School of Medicine, University of Gaziantep E-posta: bayram@gantep.edu.tr. TTS 10 th Annual Congress, Antalya, 25-29 April 2007. Contents.

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Hasan Bayram, MD, PhD. Department of Chest Diseases, School of Medicine, University of Gaziantep

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  1. From Bench to Bedside; What Should a Physician Know About Air Pollution and How to Help the Patient Hasan Bayram, MD, PhD. Department of Chest Diseases, School of Medicine, University of Gaziantep E-posta: bayram@gantep.edu.tr TTS 10th Annual Congress, Antalya, 25-29 April 2007

  2. Contents • Air pollution; definition • Effects on health • Epidemiological studies • In vivo studies • In vitro data • Intervention and effects • Suggestions • Informing patients; authorities, press, physician • Medication

  3. What is Air Pollution? • Presence of pollutants in the environment, where can have negative effects on nature and public health • Outdoor air pollution; particulate matter (PM0.5, 2.5, 10), ozone, NOx, SO2

  4. Indoor Air Pollution • NOx, Ozone, CO • PM,volatile organic compounds, • Poly aromatic hydrocarbons, • Formaldehyde, • Radon, • Biological agents, • Asbestos • Lead etc

  5. Contents • Air pollution; definition • Effects on health • Epidemiological studies • In vivo studies • In vitro data • Intervention and effects • Suggestions • Informing patients; authorities, press, physician • Medication

  6. Effect of a 10g/m3 PM2.5 Increase on Cardiovascular and Respiratory Mortality in Metropolitan Cities in USA (1979-83, 99-00) Pope CA,et al. Circulation 2004.

  7. Ozone - Mortality, APHEA-2 (23 Cities in Europe) 1h Ozone – Daily Mortality in Summer Period Gryparis A et al, Am J Respir Crit Care Med, 2004

  8. Association of Total and Respiratory Mortality with NO2 Over 6 days Over All Cities in Europe-APHEA-2. Total Mortality Resp Mortality Samoli E, et al. Eur Respir J 2006.

  9. Association of 10g/m3 increase in PM10-13/TSP With Emergency Room Visits Due to Asthma+COPD (>65y) -APHEA-2. Atkinson RW, et al. Am J Respir Crit Care Med 2001.

  10. Effect of Air Pollution on Emergency Room Visits in Denizli City Centre • Assoc. of Previous wk SO2 (r = 0,25) and PM (r=0,1) levels with emerg. visits • Effect of 100g/m3/day SO2 (1.38;1.13- 1.63) and PM (1.14;1.03-1.25) • İncrease on risk of emergency room visits Fişekçi et al Eur Respir J. (Suppl 30) 1999

  11. Monthly Emergency Room Visits Due to Asthma and Levels of SO2 and PM in Ankara SO2 - AB PM - AB Berktaş M ve Bircan A,Tüberküloz ve Toraks Dergisi 2003

  12. Association Between Respiratory Outpatients Visits and Hospitalisation and levels of SO2 (g/m3) and PM (g/m3) in Diyarbakır 2004. Bayram H, et al. Proc Am Thorac Soc 2006; 3: A389.

  13. Exercise and Asthma and Ozone- A Children Cohort • 3535 Children (9-16yr) without asthma • 5 years follow up in Southern California • Newly diagnosed asthma in 265 children • In presence of ozone, • The risk of asthma in children having exercise 2-3 times/day was 3.3 (1.9-5.8) • No effects of exercise • Time spent outside has effect McConnel R, et al. Lancet 2002

  14. Prevalence of All. Rhinitis Symptoms in High School Students in Bayrampaşa and Beykoz • N=386 • Bayrampaşa; All Rinitis= 22.8 % • Beykoz; 6%, • The risk of living in Bayrampaşa= OR:4.6 (2.3-9.0) Keleş N, et al. Am J Rhinol, 1999.

  15. FEV1 Growth in Girls/Boys Living in S California and Mean NO2 Levels in 1993-2001 Gauderman WJ, et al. N Engl J Med 2004

  16. Air Pollution and Life Quality in Asthmatics in Gaziantep • Air pollution  • Use of bronchodilators in moderate persistent asthma  • Night symptoms  Bozkurt Aİ, TTS 2. Congress Abstract Book, 1998

  17. Epidemiological Data-Summary • Mortality: Heart, lung and others • Hospital visits: Asthma, COPD, cardiac diseases • Increase in prevalence of allergic rhinitis, asthma, lung cancer, COPD, • Effect on lung growth in children • Effects on medication

  18. Contents • Air pollution; definition • Effects on health • Epidemiological studies • In vivodata • In vitro data • Intervention and effects • Suggestions • Informing patients; authorities, press, physician • Medication

  19. A human exposure hood developed for aerosol exposure Karolinska University Hospital, Stockholm (Liden et al, 1998)

  20. Air Pollutants – Clinical Effects • Irritation in mouth and nose, • Dyspnoea, wheezing, chest tightness, • Decrease in lung function tests (FEV1, FVC, FEF25-75) • Increase in airway hyperresponsiveness Brunekreef B, Holgate ST. Lancet 2002; 360: 1233-42. Peden DB. Allergy 1997; 52 (suppl 38): 37-44.

  21. Ozone – Human Exposure • Airway permeability; LDH, total protein, albumine • BAL; • PMN leukocytes ↑ • IL-6, IL-8, GM-CSF and fibronectin ↑ • Asthmatics; increase in eosinophils and MPO Scannell C, et al.Am J Respir Crit Care 1996; 154: 24-9. Balmes JR, et al. Res Rep Health Eff Inst 1997; 78:1-37.

  22. Ozone – Bronchial Epithelial GM-CSF Expression in Mild Asthmatics Hava 0.2ppm O3 (2h) Bosson J, et al. Clin Exp Allergy2003;33:777-82.

  23. Nitrogen Doxide (NO2) Exposure • Healthy subjects; Increase of neutrophils, IL-6, IL-8, and decreases in mucociliary cleareance Devlin RB,et al. Inhal Toxicol 1999; 11:89-109. • Asthmatics; Increases in Thromboxane B2 and prostaglandin D2 in BAL Jörres R, et al. Eur Respir J 1995; 8: 416-24.

  24. Effects of NO2 and SO2 on Airway Response of Asthmatics to Allergens p<0.05 Allergen (CBU x 103) 10 6 5 4 3 2 1 Air NO2 SO2 NO2 +SO2 Devalia JL, et al. Lancet 1994; 344: 1668-1671.

  25. Bronchial lavage; Neutrophil, Lymphocyte, IL-8 Bronchial biopsy; IL-8 mRNA, p selectine, VICAM-1 Diesel Exhaust Exposure (PM10=108g/m3- 2h) – Normals Stenfors N, et al. Eur Respir J 2004;23:82-6

  26. Effect of Nasal DEP (0.3mg) on Allergen Induced IgE IgE (U/ml) 160 120 allergen + DEP 80 allergen 40 0 Day 0 Day 1 Day 4 Day 8 Day 8 Diaz-Sanchez D. Allergy 1997; 52 (suppl 38): 52-56.

  27. Single Animal Exposure Units for Rodents CH Technologies(USA) Inc.http://www.toxics.com/expose/expose.html

  28. Effect of Diesel Exhaust (30-1000g/m3 PM, 7 days) on RSV Infection in Mice Harrod KS, et al. Am J Respir Cell Mol Biol 2003;28:451-63.

  29. Summary: In Vivo Laboratory Studies • Bronchospasm, airway reactivity and related clinical symptoms • Airway inflammation • Enhances effects of allergens • Potentiates effects of each others • Tendency to viral airway disease (animal studies)

  30. Contents • Air pollution; definition • Effects on health • Epidemiological studies • In vivo studies • In vitro data • Intervention and effects • Suggestions • Informing patients; authorities, press, physician • Medication

  31. Cells outgrow from tissue explant (Hoffman Modulation Contrast Light Microscope, x300)

  32. Cell Cultures (Humans, Animal) • Cell line • Primary cell cultures • Nasal, tracheal, bronchial, alveolar epithelial cells • Smooth muscle cells • Fibroblasts • Alveolar macrophages

  33. Ozone – BEC Culture Permeability of Asthmatics and Non-asthmatics Non-asthmatics Asthmatics Bayram H, et al. Clin Exp Allergy 2002.

  34. Effect of ozone on release of GM-CSF from BEC of non-asthmatics and asthmatics Bayram H, et al. J Allergy Clin Immunol 2001.

  35. Effect of Loratadine on 400ppb NO2-induced releaseof RANTES and sICAM-1 from HBEC Air 400ppb NO2 0.25M 2.5M 25M Loratadine[M]+NO2 Air 400ppb NO2 0.25M 2.5M 25M Loratadine[M]+NO2 Bayram H, et al; J Allergy Clin Immunol 1999.

  36. Incubation of BEC with DEP

  37. Effect of DEP on Ciliary Beat Frequency ofBronchial Epithelial Cells Bayram H, et al. Am J Respir CellMol Biol 1998.

  38. Effect of DEP on Release of IL-8 from Bronchial Epithelial Cells of Non-asthmatics and Asthmatics After 24hrs Non-asthmatics Asthmatics Bayram H, et al. J Allergy Clin Immunol 1998.

  39. Effect of DEP (10g/ml) on A549 cell proliferation SF • NAC (10mM) • JNK inh. (33M) Bayram H et al, Eur Respir J 2006

  40. Effect of DEP (10g/ml) on A549 cell apoptosis SF *P<0.05 and **P<0.005 vs SF Bayram H et al, Eur Respir J 2006

  41. NAC • JNK inh. • NF-kB inh. O3, NO2, DEP CBF permeability Allergen Prolif. Apoptosis (Starvation) ICAM-1  IL-8  RANTES  GM-CSF  • Anti-infl agn Adhesion molecule) ICAM-1 VCAM-1 E-selectin Eosinophil Chemotaxis Survival Mast Cell Endothelial cell

  42. Contents • Air pollution; definition • Effects on health • Epidemiological studies • In vivo studies • In vitro data • Intervention and effects • Suggestions • Informing patients; authorities, press, physician • Medication

  43. The Death Rates in Dublin 6yrs Before and After Ban (1990) on Coal Sales *Adjusted for temperature, humidity, resp epidemics and standard death rates Clancy L et al, Lancet 2002

  44. Acute Asthma Attacks Before and During Atlanta 1996 Summer Olympics * 21 June-18 July and 5 August -1 September 1996 † 19 July - 4 August 1996. Friedman MS et al. JAMA, 2001.

  45. Effect of Natural Gas Instillation on Symptoms of Rhinitis in High School Students in Istanbul (Doğal gazdan önce) (Doğal gazdan sonra) RhinitisSymptoms: 62.5% (n=125)* 51% (n=102) OR : 1.6 (1.08-2.58) *p<0.05 Keleş N, et al. Arch Environ Health 1999.

  46. Effects of Home Preventative Measures (allerg, smoke) onAsthmatic Symptoms of Children (n=937) Morgan WJ, et al. New Eng J Med 2004

  47. Effects of Improvement in Household Stoves on Riskof COPD in China (Xuanwei) (Retrospektive cohort, 1976-92) Chapman RS, et al, BMJ 2005; 331: 1050-56

  48. Contents • Air pollution; definition • Effects on health • Epidemiological studies • In vivo studies • In vitro data • Intervention and effects • Suggestions • Informing patients; authorities, press, physician • Medication

  49. Legislative Measures • 1930; Umumi Hıfzısıhha K, Gayrı Sıhhi M, regulation on environmental health • 1961; Monitory of SO2 and smoke in Ankara • 1983; Environmental protection law • 1986; Turkish Law of Air Quality Protection Ministry of Envronment and Forestry (www.cevreorman.gov.tr) and Health (www.rshm.gov.tr), Republic of Turkey.

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