What are the Human Health What are the Human Health Effects of Air Pollution?Effects of Air Pollution?

Nova Scotia Department of Environment and Nova Scotia Department of Environment and LabourLabourOutdoor Air Quality ForumOutdoor Air Quality Forum

Four Points Sheraton Hotel, HalifaxFour Points Sheraton Hotel, HalifaxMarch 8 2006March 8 2006

Dr. Judy GuernseyDr. Judy Guernsey

Department of Community Health and EpidemiologyDepartment of Community Health and Epidemiology

Dalhousie UniversityDalhousie University

IntroductionIntroduction

•• Significant advances in knowledge regarding Significant advances in knowledge regarding effects of air pollutants on health in past few effects of air pollutants on health in past few yearsyears

•• Public, especially those with respiratory Public, especially those with respiratory problems, generally aware that adverse problems, generally aware that adverse respiratory effects result from poor air qualityrespiratory effects result from poor air quality

•• Conventionally measured pollutants include Conventionally measured pollutants include groundground--level ozone, suspended particulate level ozone, suspended particulate matter, carbon monoxide, nitrogen dioxides, matter, carbon monoxide, nitrogen dioxides, sulfur dioxide and reduced sulfur compounds sulfur dioxide and reduced sulfur compounds such as hydrogen sulfidesuch as hydrogen sulfide

IntroductionIntroduction

•• Air pollutants derive from a variety of sources Air pollutants derive from a variety of sources and are classified according to chemical and are classified according to chemical composition, size and mode of release composition, size and mode of release

•• Distinctions between primary and secondary Distinctions between primary and secondary pollutants and gaseous and particulate pollutants and gaseous and particulate pollutants relevant to understanding pollutants relevant to understanding mechanisms of adverse health effectsmechanisms of adverse health effects

•• While primary route of exposure to airborne While primary route of exposure to airborne pollutants is via respiration, air pollutants can pollutants is via respiration, air pollutants can extend their effects to organ systems beyond extend their effects to organ systems beyond lungslungs

Respiratory System Respiratory System –– Brief ReviewBrief Review

•• major function of major function of lungs is gas lungs is gas exchangeexchange

•• lungs are also the lungs are also the site of some site of some biotransformationbiotransformation

•• lungs receive entire lungs receive entire cardiac output from cardiac output from right heart via the right heart via the pulmonary arterypulmonary artery

•• oxygenated blood oxygenated blood leaves the lung via leaves the lung via the pulmonary veinthe pulmonary vein

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Asthma.html

conducting airways

gas exchange region

Respiratory System Respiratory System –– Brief ReviewBrief Review ••Respiratory Respiratory bronchioles and bronchioles and pulmonary pulmonary compartment compartment comprise the gas comprise the gas exchange zoneexchange zone

••As air progresses As air progresses down the respiratory down the respiratory tract, velocity reduces tract, velocity reduces markedly as cross markedly as cross sectional area sectional area increases markedlyincreases markedly

••Gases can penetrate Gases can penetrate to gas exchange zone; to gas exchange zone; there is differential there is differential particulate matter particulate matter deposition according deposition according to particle sizeto particle size

Respiratory System Respiratory System –– Brief ReviewBrief Review•• velocity affects suspended particulate deposition as velocity affects suspended particulate deposition as

air traverses through the lungair traverses through the lung•• coarse particlescoarse particles (2.5 (2.5 --10 microns in diameter 10 microns in diameter

(including liquid aerosols)) largely (including liquid aerosols)) largely depositeddeposited in upper in upper airways and unlikely to penetrate into alveoliairways and unlikely to penetrate into alveoli

•• as air passes across airway bifurcations, there is as air passes across airway bifurcations, there is further further impactionimpaction

•• fine particlesfine particles (<2.5 microns in diameter) penetrate into (<2.5 microns in diameter) penetrate into alveolialveoli

•• diminished airway velocity corresponds with diminished airway velocity corresponds with increased particulate increased particulate sedimentationsedimentation

•• macrophages scavenge larger particles (0.1macrophages scavenge larger particles (0.1--2.5 2.5 microns)microns)

•• ultrafineultrafine particlesparticles (<0.1 microns) are able to traverse (<0.1 microns) are able to traverse membranes and be absorbed into blood stream and membranes and be absorbed into blood stream and general systemic circulationgeneral systemic circulation

Pulmonary macrophage from a coal miner’s lung

The ease with which oxygen and carbon dioxide can pass between air and blood is clear from this electron micrograph of two alveoli (Air) and an adjacent capillary from the lung of a laboratory mouse. Note the thinness of the epithelial cells (EP) that line the alveoli and capillary (except where the nucleus is located). At the closest point, the surface of the red blood cell is only 0.7 µm away from the air in the alveolus.

Possible Mechanisms of PollutantPossible Mechanisms of Pollutant--Associated Health Effects Associated Health Effects

1.1. PMPM-- oror-- ozone induced pulmonary ozone induced pulmonary inflammation (irritation or fibrosis)inflammation (irritation or fibrosis)

2.2. Free radical and oxidative stress generation Free radical and oxidative stress generation by transition metals and organic chemical by transition metals and organic chemical compounds (e.g. PAH)compounds (e.g. PAH)

3.3. Covalent modification of key intracellular Covalent modification of key intracellular proteins (e.g. enzymes)proteins (e.g. enzymes)

4.4. Biological compounds, such as Biological compounds, such as endotoxinendotoxinand and glucansglucans, which induce inflammation , which induce inflammation and innate immune effectsand innate immune effects

Possible Mechanisms of PollutantPossible Mechanisms of Pollutant--Associated Health Effects Associated Health Effects

5.5. Stimulation of autonomic nervous system Stimulation of autonomic nervous system activity, which regulates heart rate activity, which regulates heart rate variability and airway reactivityvariability and airway reactivity

6.6. Adjuvant effects in the immune system Adjuvant effects in the immune system (e.g. diesel exhaust particulates and (e.g. diesel exhaust particulates and transition metals enhancing responses to transition metals enhancing responses to common environmental allergens)common environmental allergens)

7.7. ProcoagulantProcoagulant activity by activity by ultrafineultrafine particles particles after access to the systemic circulationafter access to the systemic circulation

8.8. Suppression of normal defense Suppression of normal defense mechanisms (e.g. suppression of alveolar mechanisms (e.g. suppression of alveolar macrophage functions)macrophage functions)

Possible Mechanisms of PollutantPossible Mechanisms of Pollutant--Associated Health Effects Associated Health Effects •• Oxidative stressOxidative stress is defined as a depletion of is defined as a depletion of

intracellular glutathioneintracellular glutathione-- leading to an accumulation of leading to an accumulation of oxidized glutathione oxidized glutathione

•• Glutathione is a small protein which exists in a reduced Glutathione is a small protein which exists in a reduced state that acts as an state that acts as an antioxidantantioxidant and protects cells from and protects cells from toxins such as toxins such as free radicalsfree radicals (unprotected electrons)(unprotected electrons)

•• When glutathione is not available, an increase in When glutathione is not available, an increase in circulating free radicals occurs that in turn increases circulating free radicals occurs that in turn increases the propensity for the propensity for airway inflammationairway inflammation, increased , increased susceptibility for infectionsusceptibility for infection, and , and asthmaasthma

•• Because some people have deficiencies in their Because some people have deficiencies in their enzymes that revert glutathione from the oxidized state enzymes that revert glutathione from the oxidized state to the reduced state, these individuals may be more to the reduced state, these individuals may be more prone to experience adverse health effects during prone to experience adverse health effects during pollutant exposure compared to persons with normal pollutant exposure compared to persons with normal antioxidant defense.antioxidant defense.

Particulate matter (PM)Particulate matter (PM)

Particulate matter (PM)Particulate matter (PM)•• Comprises a complex mixture of dusts generated by Comprises a complex mixture of dusts generated by

mechanical abrasion or through combustion mechanical abrasion or through combustion processesprocesses

•• About twoAbout two--thirds of PMthirds of PM2.52.5 formed from precursor formed from precursor gasesgases

•• These aspects makes investigations more These aspects makes investigations more challenging (exposure assessment, size challenging (exposure assessment, size characterization)characterization)

•• PM can initiate tissue damage and alter defense PM can initiate tissue damage and alter defense mechanisms of the body against foreign materialsmechanisms of the body against foreign materials

•• Some of the adverse health effects include Some of the adverse health effects include development of respiratory disease, such as chronic development of respiratory disease, such as chronic bronchitis, increased risk for respiratory symptoms bronchitis, increased risk for respiratory symptoms and declines in lung functionand declines in lung function

Particulate matter (PM)Particulate matter (PM)•• Many studies have shown a consistent relationship between Many studies have shown a consistent relationship between

PM10, PM2.5 and mortality as well as hospital admissions and PM10, PM2.5 and mortality as well as hospital admissions and ER visitsER visits

•• Some investigations have linked PM to lung cancerSome investigations have linked PM to lung cancer•• Numerous studies linking cardiovascular disease, chronic Numerous studies linking cardiovascular disease, chronic

obstructive lung disease and pneumonia in persons over 65 obstructive lung disease and pneumonia in persons over 65 with exposure to PMwith exposure to PM1010

•• Longer term exposure has been associated with increased Longer term exposure has been associated with increased mortality and lower birth weights; a just published study of mortality and lower birth weights; a just published study of Nova Scotia infants has reported no significant relationships Nova Scotia infants has reported no significant relationships between first trimester exposure to PM10, SO2 and ozone after between first trimester exposure to PM10, SO2 and ozone after adjusting for birth yearadjusting for birth year

•• The cardiovascular mortality association was highlighted in The cardiovascular mortality association was highlighted in recent reanalysis of 1952 London smog episode datarecent reanalysis of 1952 London smog episode data

•• Causal components of relationship between particulate matter Causal components of relationship between particulate matter and cardiovascular morbidity and mortality remain to be and cardiovascular morbidity and mortality remain to be identified and current studies are unable to define a threshold identified and current studies are unable to define a threshold of no health effectsof no health effects

•• Hence WHO has recommended against establishing a guideline Hence WHO has recommended against establishing a guideline value for PM and suggests instead that risk managers use value for PM and suggests instead that risk managers use linear, no threshold health functions for setting air quality linear, no threshold health functions for setting air quality targetstargets

Particulate Matter Particulate Matter -- UFPUFP•• There is now sufficient reason to believe that There is now sufficient reason to believe that ultrafineultrafine

particles (UFP) are important in morbidity and mortality particles (UFP) are important in morbidity and mortality fractions previously attributed to largerfractions previously attributed to larger--size fractionssize fractions

•• Reasons for potential importance include: high Reasons for potential importance include: high pulmonary deposition efficiency, magnitudes higher pulmonary deposition efficiency, magnitudes higher particle number concentrations than larger particles, particle number concentrations than larger particles, ability to carry large amounts of absorbed or condensed ability to carry large amounts of absorbed or condensed toxic air pollutants (oxidant gases, organic compounds, toxic air pollutants (oxidant gases, organic compounds, transition metals)transition metals)

•• A study to examine the chemical composition of UFP in A study to examine the chemical composition of UFP in southern California noted the trace elements included southern California noted the trace elements included lead, arsenic, zinc, gold and silver and a range of other lead, arsenic, zinc, gold and silver and a range of other transition metalstransition metals

•• Most of the trace element particles detected in this study Most of the trace element particles detected in this study were within a range of 0.01were within a range of 0.01--1.0 micron1.0 micron

Ammonium is a measurable fraction of the fine particle mass across Canada (10-20%).

There is evidence that reductions in ammonia air concentrations will lead to a decrease in fine particle mass, particularly in winter

-- Bob Vet, Meteorological Service of Canada, 2003Bob Vet, Meteorological Service of Canada, 2003

Ammonia and air quality – Recent evidence

Ammonia Released to Air in Canada, 1995

Other6%

Agriculture (Livestock)52%

Light-Duty Gasoline Vehicles

2%

Forest Fires3%

Chemicals Industry4%

Fertilizer Application33%

OzoneOzone•• Generated almost entirely from precursor gases Generated almost entirely from precursor gases

((NOxNOx))•• Our current understanding of how ozone exerts its Our current understanding of how ozone exerts its

adverse health effects has been generated mainly by adverse health effects has been generated mainly by ozone exposure studies of healthy and asthmatic ozone exposure studies of healthy and asthmatic individualsindividuals

•• These have consistently demonstrated a decrease in These have consistently demonstrated a decrease in forced vital capacityforced vital capacity (e.g. ability to blow air out of (e.g. ability to blow air out of your lungs) and your lungs) and forced expiratory volumeforced expiratory volume at 1 at 1 secondsecond (FEV1) (a measure of airways constriction) (FEV1) (a measure of airways constriction) associated with chest discomfort on inspiration and associated with chest discomfort on inspiration and increased nonspecific airway increased nonspecific airway hyperresponsivenesshyperresponsiveness. .

•• High level exposure in lower lung can result in High level exposure in lower lung can result in congestion, hemorrhage and pulmonary edema congestion, hemorrhage and pulmonary edema (rare)(rare)

OzoneOzone

•• Ozone exposure ranging from 100 to 400 ppb is Ozone exposure ranging from 100 to 400 ppb is traditionally accompanied with traditionally accompanied with neutrophilicneutrophilicinflammation in the alveoli as early as one hour after inflammation in the alveoli as early as one hour after exposure and can persist for up to 24 hoursexposure and can persist for up to 24 hours

•• Ozone exposure of less than 500 ppb without Ozone exposure of less than 500 ppb without exercise typically has no effect on lung function; exercise typically has no effect on lung function; however ozone exposure with exercise results in however ozone exposure with exercise results in increased breathing frequency, decreased FEV1 and increased breathing frequency, decreased FEV1 and FVC and an increase in airways resistance and FVC and an increase in airways resistance and symptoms.symptoms.

•• Hence outdoor exercise on days in which air quality Hence outdoor exercise on days in which air quality is poor should be avoided by susceptible individualsis poor should be avoided by susceptible individuals

OzoneOzone•• Ozone has been significantly associated with mortality, Ozone has been significantly associated with mortality,

hospital admissions and ER visits, however less consistent hospital admissions and ER visits, however less consistent mortality results are observed in winter months when ozone mortality results are observed in winter months when ozone levels are lowerlevels are lower

•• Links have also been observed between chronic ozone Links have also been observed between chronic ozone exposure and lung cancer with more significant effects in exposure and lung cancer with more significant effects in malesmales

•• Ozone toxicity occurs in a dose dependent fashion with no Ozone toxicity occurs in a dose dependent fashion with no observable thresholdobservable threshold

•• Based on this evidence, the WHO declared it is not possible to Based on this evidence, the WHO declared it is not possible to assign an air quality guideline but rather that an acceptable riassign an air quality guideline but rather that an acceptable risk sk level would need to be chosen by considering the lower level would need to be chosen by considering the lower frequency of responders in the population and reduced severity frequency of responders in the population and reduced severity of response at lower levels of exposureof response at lower levels of exposure

Sulfur dioxide, nitrogen dioxide and Sulfur dioxide, nitrogen dioxide and carbon monoxidecarbon monoxide•• Exposure (5 min) to inhaled SOExposure (5 min) to inhaled SO2 2 induces rapid onset induces rapid onset

bronchoconstrictionbronchoconstriction in both healthy (>5 in both healthy (>5 ppmppm) and ) and asthmatic people (>0.25 asthmatic people (>0.25 ppmppm) but full recovery ) but full recovery occurs within 30 minutes post exposure though for occurs within 30 minutes post exposure though for asthmatics this takes longerasthmatics this takes longer

•• A recent study found that SOA recent study found that SO2 2 exposure was exposure was associated with increased hospitalizations for associated with increased hospitalizations for asthma in children but not in adults or individuals asthma in children but not in adults or individuals with other respiratory conditionswith other respiratory conditions

•• Ambient SOAmbient SO2 2 might contribute to acid aerosol might contribute to acid aerosol formation and could be important because some formation and could be important because some studies suggest that asthma symptoms are studies suggest that asthma symptoms are increased on days with high aerosolized acid levelsincreased on days with high aerosolized acid levels

•• Exposure to ozone or cold dry air before exposure to Exposure to ozone or cold dry air before exposure to SO2 increases bronchial sensitivity to SO2 in SO2 increases bronchial sensitivity to SO2 in asthmatic patientsasthmatic patients

Sulfur dioxide, nitrogen dioxide and Sulfur dioxide, nitrogen dioxide and carbon monoxidecarbon monoxide

•• NO2 is associated with pronounced decreases in pulmonary NO2 is associated with pronounced decreases in pulmonary function and increased rates of respiratory illness though it isfunction and increased rates of respiratory illness though it isdifficult to differentiate these effects from ozone related difficult to differentiate these effects from ozone related impactsimpacts

•• Because NO2 is a precursor to photochemical smog, its major Because NO2 is a precursor to photochemical smog, its major effect on health as an outdoor pollutant is likely through the effect on health as an outdoor pollutant is likely through the formation of ozone. formation of ozone.

•• High NO2 personal exposure the week before the onset of a High NO2 personal exposure the week before the onset of a respiratory viral infection has been linked to increased severitrespiratory viral infection has been linked to increased severity y of a resulting asthma exacerbationof a resulting asthma exacerbation

•• In challenge studies of healthy subjects and smokers, NO2 In challenge studies of healthy subjects and smokers, NO2 exposure induces an inflammatory response in the airways exposure induces an inflammatory response in the airways characterized by characterized by neutrophilneutrophil influx and reduced lymphocyte influx and reduced lymphocyte populationspopulations

•• Compared with its direct effects on the airways, NO2 might play Compared with its direct effects on the airways, NO2 might play a more prominent role as a sensitizing agent to inhaled allergena more prominent role as a sensitizing agent to inhaled allergen

•• Despite these results, WHO recently concluded that NO2 Despite these results, WHO recently concluded that NO2 effects observed in effects observed in epiepi studies may be attributable to other studies may be attributable to other pollutants, including particulate matter originating from the pollutants, including particulate matter originating from the same combustion sourcessame combustion sources

Sulfur dioxide, nitrogen dioxide and Sulfur dioxide, nitrogen dioxide and carbon monoxidecarbon monoxide

•• Recent epidemiological studies conducted Recent epidemiological studies conducted throughout the world have provided valuable insight throughout the world have provided valuable insight into the associations between SO2, NO2 and CO into the associations between SO2, NO2 and CO exposure and increases in cardiopulmonary exposure and increases in cardiopulmonary mortality, respiratory and cardiovascular hospital mortality, respiratory and cardiovascular hospital admissions, emergency admissions caused by admissions, emergency admissions caused by stroke (NO2) and myocardial infarction (NO2 and CO)stroke (NO2) and myocardial infarction (NO2 and CO)

•• Such multiSuch multi--pollutant modeling studies are still in pollutant modeling studies are still in their infancy and more work needs to be done.their infancy and more work needs to be done.

Interaction between allergens and Interaction between allergens and pollutantspollutants

•• Since 1997 studies have focused on automobileSince 1997 studies have focused on automobile--related related pollutants and concluded that high vehicle traffic is pollutants and concluded that high vehicle traffic is associated with asthma, cough, and wheeze in children associated with asthma, cough, and wheeze in children with known allergic sensitizationwith known allergic sensitization

•• EpiEpi studies investigating the role of allergenstudies investigating the role of allergen--pollutant pollutant combinations as triggers of asthmatic attacks have combinations as triggers of asthmatic attacks have revealed that ozone, NOrevealed that ozone, NO22 and aeroallergens were and aeroallergens were independently or interactively related with asthma independently or interactively related with asthma symptoms and changes in peak flow rates.symptoms and changes in peak flow rates.

•• Studies linking asthma admissions with thunderstorms Studies linking asthma admissions with thunderstorms was originally attributed to peak fungal spore counts was originally attributed to peak fungal spore counts preceding or during the weather front; more recent preceding or during the weather front; more recent investigations have shown a positive association investigations have shown a positive association between asthma admissions and higher levels of ozone between asthma admissions and higher levels of ozone during these times but failed to show the link with during these times but failed to show the link with thunderstormsthunderstorms

ConclusionsConclusions

•• Important questions:Important questions:– Does air pollution increase the risk of asthma

development?– Does air pollution exacerbate asthma or allergic

rhinitis?– Which air pollutants are most commonly associated

with adverse health effects and how can they be reduced or avoided?

– Are allergic individuals with asthma at greater risk of early death from air pollutants?

ConclusionsConclusions•• Some answers:Some answers:

– Exposure to ground level ozone has been associated with increased risk of asthma development among children in California playing outdoor sports

– Ozone can increase airway inflammation and airway responsiveness and also can potentiate the airway response to inhaled allergens

– Exposure to nitrogen oxides has been associated with an increase in respiratory infection and wheezing and can increase the effects of inhaled allergen responses

– Sulfur dioxide (SO2) in high concentrations with or without exercise is a respiratory irritant, provoking airflow limitations

– Particulate matter has been associated with a range of health outcomes; understanding of the impacts of ultrafine particles is only just beginning

ConclusionsConclusions•• Despite declines in levels of some air pollutants, Despite declines in levels of some air pollutants,

recent epidemiological studies continue to recent epidemiological studies continue to demonstrate associations between air pollution and demonstrate associations between air pollution and health problemshealth problems

•• These associations were observed even at low These associations were observed even at low exposure levels measured in Canada and elsewhereexposure levels measured in Canada and elsewhere

•• Acute exposureAcute exposure--related effects are better understood related effects are better understood than chronic disease outcomesthan chronic disease outcomes

•• Multiple pollutant interactions are just beginning to Multiple pollutant interactions are just beginning to be investigatedbe investigated

•• Still much that we do not know about the biological Still much that we do not know about the biological mechanisms that cause these health effectsmechanisms that cause these health effects

•• Air pollution still remains a significant health risk to Air pollution still remains a significant health risk to CanadiansCanadians