Health Effects of Air Pollution

1. Health Effects of Air Pollution By the Air Pollution Committee

2. Air Pollution and Its Health Effects Are Not a New Concern! Actios of Antiochenus (500-575 AD) wrote: �Irritations of the eyes, which are casued by smoke, over-heating dust, or similar injury, are easy to heal; the patient being advised first of all to avoid the irritating causes�For the disease ceases without any use of any kind of medicine, if only a proper way of living be adopted.�

3. What is Smog? A term used to describe a mixture of smoke and fog. Occurs when high concentrations of moisture is combined with smoke (often containing oxides of sulfur and nitrogen) in the presence of high temperatures or thermal inversions and the absence of wind. These conditions cause polluted air to stagnate over industrial areas causing potential respiratory health hazards. Large coastal industrial centers with surrounding high ground are more prone to smog. There is often a diurnal variation in smog formation as a necessary component for its formation is sunlight.

4. Definition of Air Pollutants Primary � pollutants directly emitted into the atmosphere (eg. SO2, some NOx species, CO, PM) Secondary � pollutants that form in the air as a result of chemical reactions with other pollutants and gases (eg. Ozone, NO2, some particulates)

5. Gaseous Pollutants NOx SO2 Ozone CO CO2 SVOC (semi-volatile organic compounds include aldehydes, dioxins, benzene, 1,3-butadiene)

6. Particulate Matter (PM) Coarse PM (2.5-10 um) - regulatory standard = PM10 Fine PM (0.1 � 2.5 um) - regulatory standard = PM2.5 Ultrafine PM (<0.1 um) - not regulated

7. Indoor Air Pollutants Sources - cooking - combustion - particle resuspension - building materials - air conditioning/cleaning - consumer products - smoking - heating - biologic agents Products - NOx, CO, CO2, SVOCs, ozone (O3-), bacteria, mold-byproducts, endotoxin

8. Outdoor Air Pollutants Sources - industrial - commercial - mobile - urban - regional - agricultural - natural Products - SO2, O3-, NOx, CO, PM, SVOC

9. NOx (pronounced "nox") Gases NO (nitric oxide) is the principal emitted NOx gas from high temperature combustion in air. - Acts a catalyst in the reactions that cause the destruction of ozone - Reacts with ozone and tropospheric radicals to help form NO2, ozone, and other secondary pollutants such as peroxyacetyl nitrate. NO2 is the lesser of the two emitted NOx gases from high temperature combustion in air. - It is an important species in the atmosphere as it absorbs in the visible wavelength region - Manifests as the �Brown Cloud� seen over large polluted cities (eg. Denver, LA, Mexico City, Beijing�) - NO2 is a precursor to photochemical smog; can be photolyzed to yield oxygen atoms that can react with molecular oxygen to create ozone (UV sunlight + hydrocarbons=ozone).

10. Sulfur Dioxide (SO2)Referred to as �SOX�  Sulfur dioxide is a major primary pollutant in the atmosphere Originates mostly from coal fired power plants and other fossil fuel combustion Sulfur dioxide is usually oxidized by ozone and hydrogen peroxide to form sulfur trioxide, a secondary pollutant that is extremely soluble in water Sulfur oxides present in the atmosphere when condensation occurs results in droplets of sulfuric acid called �acid rain�

11. Ozone (03-) O3-, absorbs UV radiation and creates a warm layer of air responsible for the thermal structure of the stratosphere O3- present in the troposphere is mainly due to man-made pollution; higher concentrations are found in urban areas O3- is formed when NOX combines with volatile organics compounds (VOC, i.e. chemical vapors) in the presence of sunlight VOC + NOx + Sunlight = Ozone O3- linked to causing new onset asthma and exacerbating pre-existing asthma

12. Particulate Matter (PM) Coarse PM (aerodynamic diameter 2.5-10um) - major sources are abraded soil, road dust from brakes and tires, construction debris, aggregation of smaller combustion particles. Fine PM (= 2.5 um) and Ultrafine PM (<0.1 um) - byproducts formed during the combustion of fossil fuel products Coarse and Fine PM have been associated with increased cardiorespiratory morbidity and mortality Much less is know about the adverse health effects of Ultrafine PM which is more abundant and potentially more toxic

13. Mechanisms Of Pollutant-Related Adverse Health Effects PM or ozone induced airway inflammation Oxidative stress induced by transition metals or polyaromatic hydrocarbons Covalent modifications of intracellular proteins/enzymes Biologic compounds (glucans, endotoxin) effect on the innate immune response and inflammation Stimulation of the autonomic nervous system Adjuvant effects (DEP + allergens) Procoagulant activity of ultrafine PM Suppression of normal defense mechanisms

17. Bronchial Hyperresponsiveness (BHR) and Air Pollutants Kreit et al1 exposed patients with and without asthma to ozone and found an increase in BHR in patients with asthma. A meta analysis of 20 studies evaluating the effect of NO2 on asthma showed a significant increase in BHR.2 1Kreit JW et al Ozone induced changes in pulmonary function and bronchial responsiveness in asthmatics. J Appl Physiol 1989;66:217-22. 2Folinsbee LJ. Does nitrogen dioxide exposure increase airway responsiveness? Toxicol Indust Health 1992;8:273-83.

18. Lung Function and Air Pollutants Inhalation of 1 ppm of SO2 for 10 minutes during moderate exercise decreased FEV1 by 23% in adolescents with asthma.1 An association between ambient ozone levels below EPA limits and asthma symptoms was found in children with asthma living in New England.2

19. ER Visits for Respiratory Complaints and Air Pollutants Numerous studies have found an association between PM 10 levels and ER visits for asthma. In Seattle, an increase of 11 �g/m3 in fine PM was associated with an 11% increase in asthma ER visits.1 Ozone and SO2 have been associated with ER visits for asthma in Mexico.2

20. Inflammatory Markers and Air Pollutants Exposure to ozone results in an influx of neutrophils and alveolar macrophages into the airway.1,2 IL-6, IL-8, LTB4, and thromboxane B2 are increased after exposure to ozone. mCD14 surface expression on airway macrophages is enhanced following ozone exposure 2 PM10 exposure increases allergen specific IgE production leading to increased airway inflammation.

21. Interactions Between Air Pollutants and Allergen Exposure to 0.12 ppm ozone decreased the amount of ragweed allergen required to provoke a 20% decrease in FEV1.1 NO2 exposure has been shown to increase airway hyperresponsiveness to tree pollen.2 Exposure to PM increases total serum IgE levels. Nasal histamine levels are increased 3-fold when diesel exhaust particles are co-administered with allergen. Exposure to airborne endotoxin enhances response to inhaled allergen3

22. Adverse Health Effects of Specific Air Pollutants

23. Diesel Exhaust Particulate (DEP) The largest single source of airborne PM is diesel exhaust. Diesel engines emit up to 100 times more exhaust particulate matter than gasoline engines. Diesel exhaust particulates consist of a carbon core with a large surface area which permits many chemicals and metals to attach. Most of the deleterious effects of DEP�s are due to the chemicals that are adsorbed onto their surface.

24. Effects of Diesel Exhaust on the Respiratory System Increased Diesel exhaust PM levels have been linked to cardiorespiratory mortality.1 Numerous studies have demonstrated an association between high air pollution levels and cough, bronchitis, asthma, and COPD. As a strong association between high diesel exhaust levels and other airborne pollutants exists, it is difficult to determine the relative contributions of each pollutant source.

25. Effects of Diesel Exhaust on the Respiratory System Physician diagnosed asthma has been reported to be more frequent among children living within 100 meters of a freeway.1 Higher rates of allergic sensitization are found in children playing more than one hour/day near major traffic thoroughfares.2

26. Adjuvant Effects of Diesel Exhaust DEP�s increase allergic inflammation when co-administered with allergens. In rat models, intra-tracheal administration of grass pollen in conjunction with DEP�s induces inflammatory reactions in the lungs characterized as macrophage and eosinophil infiltrates.1 Human B cells cultured with IL-4 and DEP�s show a 360% increase in IgE production.

27. Controlled Chamber Studies:Effects of Diesel Exhaust Healthy volunteers exposed to 300 ug/m3 diesel exhaust or DEP�s for 1 hour revealed increased PMNs in sputum and bronchial biopsies and increased IL-6, IL-8 and growth-related oncogene ? levels with minimal changes in lung function. Similar studies in patients with mild asthma have shown that DEP exposure increases airway hyper-responsiveness to methacholine and airway resistance.1

28. Effects of Diesel Exhaust In Vivo Human Data Subjects challenged nasally with 0.3 mg of DEP�s showed increased IgE isotype switching with increased IgE levels.1 DEP�s, when co-administered with allergen, cause an increase in TH2 cytokines and a decrease in IFN-g. Dust mite sensitive patients challenged with dust mite allergen and DEP�s have three-fold increases in nasal histamine levels.2 Fujieda et al Am J Resp Cell Mol Bio 1998;19:507-12. Diaz � Sanchez et al JACI 2000;106:1140-6.

29. Diesel Exhaust Particulate Increases The Rate Of Sensitization To A Novel Allergen Repeated nasal immunization with a neoantigen results in increased production of specific IgG and IgA If subjects are exposed to DEP�s before each neoantigen exposure then 60% of the subjects produced a specific IgE response to the neoantigen Rechallenge of patients months later with the neoantigen resulted in typical symptoms of allergic rhinitis

30. Summary of Clinical Features of Diesel Exhaust Particles

31. Mechanisms of DEP�s Effects Inflammation associated with asthma in the presence or absence of DEP�s is coupled with the production of reactive oxygen species. Macrophages and epithelial cells generate reactive oxygen species (superoxide and hydrogen peroxide) upon exposure to DEPs. N-acetylcysteine, an antioxidant, is known to suppress the effects of DEP on macrophages. Patients with decreased antioxidant responses may be more susceptible to asthma and the effects of diesel exhaust.

32. Genetic Susceptibility to the Effects of DEP Glutathione is the main intracellular antioxidant produced by the human body. Individuals with gene variants for phase II detoxifying enzymes (Glutathione-S-transferase P1 and M1) causing the absence or reduced production of these enzymes have increased susceptibility to the adjuvant effects of DEP

33. Ozone

34. Controlled Chamber Studies Ozone exposure studies depends on the concentration, duration of exposure and degree of exercise Ozone exposure in healthy human volunteers results in decreased FVC and FEV1, inspiratory chest dyspnea and increased BHR Ozone exposures between 0.1 to 0.4 ppm are associated with neutrophilic inflammation after 1 hour that can persist up to 24 hours

35. Ozone (cont.) Ozone worsens airflow in asthmatic patients greater than in normal healthy volunteers One study demonstrated that levels as high as 0.4 ppm had no effect on individuals with EIB

36. Ozone Enhances Allergic Inflammation Ozone causes an increased immediate and late airway response to inhaled allergen Increased sputum eosinophils were observed in induced sputum after 6 hours This effect was most pronounced at higher ozone exposure levels (0.16-.25 ppm) Allergic asthma patients challenged intranasally with dust mite allergen + 0.4 ppm ozone had increased ECP and IL-8 levels after 8 hours

37. Sulfur Dioxide, Nitrogen Dioxide, Carbon Monoxide Epidemiologic studies have demonstrated that exposure to SO2, NO2 and CO increase cardiopulmonary mortality, respiratory and cardiovascular hospital admissions caused by stroke (NO2) and myocardial infarction (NO2 and CO)

38. Sulfur Dioxide Controlled exposure studies (5 min) to inhaled SO2 induces rapid onset bronchocontriction in healthy and asthmatic subjects Asthmatic patients experience increased symptoms and a greater decrease in lung function at lower concentrations (0.25 ppm) compared to healthy volunteers that are unresponsive at concentrations less than 0.5 ppm Exposed asthmatic patients are refractory to the effects of SO2 for up to 4 hours after exposure Exposure to ozone or cold air before SO2 exposure increases BHR to SO2 in asthma patients

39. Sulfur Dioxide: Genetic Susceptibility TNF-? promoter polymorphism was found in asthma patients who were spirometrically responsive to inhaled SO2 (FEV1>12%)

40. Nitrogen Dioxide Most likely health effect as an outdoor pollutant is through the formation of ozone High NO2 exposure (0.02 ppb) 1 week before a respiratory URI has been associated with increased asthma exacerbations Healthy subjects and smokers exposed to NO2 (2-6ppm) manifest increased PMNs in the airways and reduced lymphocyte subpopulations Exposure to 0.4 ppm NO2 for 4 hours enhances the immediate and late phase response to inhaled allergen

41. Interaction Between Allergen And Pollutants Epidemiologic studies of pollution and aeroallergens on causing asthma Epidemiologic studies of pollution and aeroallergens on the exacerbation of asthma Experimental studies on the adjuvant effects of DEPs on specific TH2 responses Role of pollution and global warming on natural allergen production

42. Epidemiologic Studies Of Pollution And Aeroallergens On Causing Asthma Many studies have investigated the effects of automobile related pollutants in heavily traveled expressways on causing asthma symptoms in allergic children High vehicle traffic is associated with asthma symptoms in children with known allergen sensitization

43. Epidemiologic Studies Of Pollution And Aeroallergens On Asthma Exacerbation Ozone and fungal spores have been demonstrated to be cofactors in increasing asthma symptoms and SABA use Ozone, NO2 and SO2 individually or in combination may enhance airway response to inhaled allergens

44. Experimental Studies On The Adjuvant Effects Of DEPs On Specific Th2 Responses DEPs synergize with allergen to enhance specific allergen IgE production by promoting TH2 cytokine production These observations may account for the worldwide rising prevalence of asthma which is concurrent with the rapid increase of diesel powered transportation

45. Role Of Pollution And Global Warming On Natural Allergen Production  Climate change has been demonstrated to cause ragweed plants to grow faster, flower earlier and produce greater amounts of pollen This effect was greater in urban areas where CO2 levels and temperatures were higher compared to rural areas Doubling the atmospheric concentration of CO2 in ragweed pollen production by 61%

46. Interventions on the Health Effects of Air Pollution Public health measures to decrease air pollutant levels improve respiratory outcomes. In Dublin, Ireland a ban on bituminous coal sales in in 1990 after 72 months resulted in a:1 - 70% decrease in black smoke concentrations - 5.7% decrease in non-trauma death rates - 15.5% decrease in respiratory death rates - 10.3% decrease in cardiovascular death rates

47. Treatment Of The Health Effects Of Air Pollution Inhaled corticosteroids (fluticasone) has been shown to decrease the effect of SO2 and NO2 on allergen induced bronchial inflammation. Leukotriene modifying drugs have not been studied for their prophylactic effects on air pollution.

48. What Is The Role Of The Allergist? Understand the scientific data that supports the adverse role of air pollution on airway diseases such as asthma Be familiar with exposure guidelines for gaseous and particulate matter air pollutants Know the sources of outdoor and indoor air pollutants Support societal control of air pollution through conservation and efforts to improve air pollution standards

49. Pollutants Sources NO2 Outdoor: automobiles, burning fossil fuels Indoor: gas appliances, kerosene heaters, wood stoves, tobacco products (side stream smoke) SO2 Heating fuels, coal fired plants PM10 Diesel engines, fossil fuels O3 Created when sunlight reacts with NO2

50. EPA Standards for Air Pollutants

52. Air Quality Index If the air quality value is below 32, the air quality is considered relatively good. If the AQI value is in the range of 32 to 49 (moderate category), there may be some adverse effects on very sensitive people. An index value in the 50 to 99 range (poor category), may have some short-term adverse effects on the human or animal populations, or may cause significant damage to vegetation and property. An AQI value of 100 or more (very poor category) may cause adverse effects on a large proportion of those exposed.

53. What Is A Smog Alert? Smog Watch is when there is a 50 per cent chance that a smog day is coming within the next three days. Smog Advisory is when there is a strong likelihood that a smog day is coming within the next 24 hours or if a smog day has happened without warning, or is about to occur. Termination notice is issued once a smog advisory is over.

54. What Should We Advise Patients With Respiratory Diseases? Minimize outdoor activities during poor air quality days Advise against living in areas near high automobile traffic, power plants or chemical manufacturing plants Environmental control measures (keep windows close, run A/C, filtration�)

55. Resources www.EPA.gov www.airqualityontario.com www.aaaai.org Air Pollutants and the Respiratory Tract 2nd Ed. Eds. W. Michael Foster and Daniel L. Costa. Health Effects of Air Pollution Rostrum. J Allergy Clinical Immunology 2004;114:1116-23.