1. AIR POLLUTION AND HEART DISEASE
Speaker : Dr Anunay Gupta

2.  Introduction and History
 Air Pollution: PM, Gaseous, VOC
 Outdoor Pollution: Diesel/Petrol/CNG
 Indoor Pollution: Cigarette/CO/Angeethi
 Pathophysiology of Pollution and CAD (Animal studies)
 Pollution and CVD Evidence (Clinical studies)
 Pollution in India/Delhi
 Summary

3. INTRODUCTION
 Lungs were considered to be the primary target affected by air pollution
 Over past decade, effects on CVS have become a focus of research
 Exposures to particulate matter (PM) in air at or below the current
quality standards has been found to significantly increase CVD morbidity
and mortality
Boris Z. Simkhovich et al Curr Opinion in Cardiology 2009

4. INTRODUCTION
 Traditional risk factors account for majority of Ischemic cardiac events
 Increasingly recognized as an important and modifiable risk factor
 Global Burden of Disease Report: Particulate air pollution is estimated to
cause 3.1 million deaths a year and 22% of disability adjusted Life years
(DALY) due to IHD
Nicholas L. Mills MD Nat Clin Pract Cardiovasc Med 2009
Lim SS et al. Lancet 2012;380:2224-60

5. HISTORICAL PERSPECTIVE
 In 1872 , Robert Angus Smith published air pollution–related study
 “Air and Rain. The Beginning of Chemical Climatology”
 Pioneered studies of air pollutants as hazardous components of urban air and
analyzed their presence in “acid rains.”

6. MAJOR EPISODES OF SEVERE AIR
POLLUTION
1930: Meuse River Valley, Belgium
• Main sources: zinc smelter, sulfuric acid factory, glass manufacturers
• 60 deaths recorded
1948: Donora, Pennsylvania
• Main sources: iron and steel factories, zinc smelting, and an acid plant
• 20 deaths observed
1952: London (KILLER FOG )
• Primary source: domestic coal burning
• 4,500 excess deaths recorded during week- long period in December
2010 : Iceland volcano
• The eruption, caused massive dislocation across Europe.
• Caused around 63,000 flights canceled in 23 European countries, stifling the lifeblood of the
continent's economy.

7. AIR
POLLUTION
Vehicle Exhaust
Industrial emissions
Natural Fires
GASEOUS
CO2
CO
NO
Ozone
SO2
VOLATILE ORGANIC
COMPOUNDS
Quinones
Polycyclic aromatic
hydrocarbons
Benzenes
Toluenes
PARTICULATE MATTER
Fine
Coarse
Ultra fine
COMPOSITION OF AIR POLLUTION

8. AIR POLLUTION
1: PARTICULATE MATTER
 Mixture of particles that adversely affect health
 Includes dust, dirt, soot, smoke, and liquid droplets
 Broadly categorized and regulated by aerodynamic diameter (μm)
 Thousands of chemicals and constituents within PM that may solely, or in
combination, impart biological harm.

9. AIR POLLUTION
1: PARTICULATE MATTER

10. Mobile Sources
(vehicles)
VOCs, NO2, PM
Stationary Sources
(power plants, factories)
NO2, SO2, PM
Area Sources
(drycleaners, gas stations)
VOCs
Natural Sources
(forest fires, volcanoes)
PM
AIR POLLUTION
1: PARTICULATE MATTER

11.  CONSTITUENTS
Organic / elemental carbon; Hydrocarbons, Ions- NH4, sulfate, nitrate
Metals- Fe, Al, Zn, Cu
 SOURCES
 Combustion sources - coal, oil, gas, wood, tree, industry
 Tobacco smoke, cooking , burning candles or oil lamps and kerosene heaters
 LIFETIME Days to weeks, distributed regionally (1000 or more km)
AIR POLLUTION
1: PARTICULATE MATTER
PM 2.5 FINE PARTICLES

12.  Exposure : Mass of particles within a volume of air
 Risk of CV disease is linear without evidence of a safe PM threshold
 Daily levels may exceed 200–500 μg/m3, equivalent to passive smoking
(e.g. smoky bars 500–1500 μg/m3)
Robert D. Brook Clinical Science (2008)
10 μg/m3 - Annual mean
25 μg/m3 - 24-hour mean
AIR POLLUTION
1: PARTICULATE MATTER
LEVELS

13.  Inhaled but deposited in the upper respiratory tract
 Generated by mechanical processes , associated with human (e.g.
agriculture) or natural (e.g. erosion) activities.
 Constituents
 Dust , Endotoxin Fungi , Debris , Ground materials
 Metals : Si , Ca , Fe
 Lifetime : hours to day , distributed over 10 – 100 kms
Nicola Martinelli ET al European Journal of Internal Medicine 2013
Guidelines Values
20 μg/m3 annual mean
50 μg/m3 24-hour mean
AIR POLLUTION
1: PARTICULATE MATTER
COARSE PM 10

14.  Diameter less than 100 nm
 Measured as number of particles per m3of air because of very large numbers, but small
overall mass
 Constituents
 Primary combustion – hydrocarbons ,metals , organic carbon
 Sources
 Traffic Related Pollution
 Fresh automobile and combustions emissions
 Lifetime - Do not last long in the air, deposit or rapidly form fine particles by coagulation.
- Minutes to hours , distributed 100s of metres
AIR POLLUTION
1: PARTICULATE MATTER
ULTRAFINE PARTICLES { PM 0.1 }

15. ULTRAFINE PARTICLES { PM 0.1 }
INCREASING IMPORTANCE !
 High number of particles; a large surface area for transporting toxic materials
 Capable of DIRECTLY translocating into the systemic circulation
 Very acute exposure to traffic for only minutes ,conveys a particularly large
CV health risk
Mills, N. L. et al Am. J. Resp. Crit. Care Med. 173,426–431

16. DETERMINANTS OF EXPOSURE
 Pollutants vary with emission rates, weather patterns, and diurnal/seasonal cycles
in solar radiation
 O3 , PM2.5 and secondary VOCs, peak in afternoon
 Nox, CO and particle elemental carbon (combustion ) peak in rush hour
 Temporal behavior; governed by formation rate and the length of time it remains
in the atmosphere
 O3 and PM2.5 have the longest lifetime and build up over multiple days and
spread, by the prevailing winds, over large geographic regions

17. INDOOR AIR POLLUTION
 Results from solid fuels, principally biomass and coal
 Ranked as one of top 10 environmental risk factors of global burden
of disease
 In developing countries, organic materials such as wood, dung, or
charcoal (biomass fuel) are burned and used for cooking, home
heating, and lighting
 The burning of solid fuels in the homes release pollutants including
respirable PM, PAHs, heavy metals

18. AIR POLLUTION:
2: GASEOUS
NITROGEN DI OXIDE SULFUR DIOXIDE
FORMS PM 2.5 and Ozone Forms PM 2.5
SOURCE combustion processes Indoor : Use of kerosene
heaters
Outdoor Burning of
fossil fuels (coal and oil)
EVIDENCE Associated with daily
hospital emergency
admissions for ACS
Sunyer et al. reported
the association of daily
SO2 levels with hospital
admissions for CVDs in
Europe
WHO. Air quality and health. WHO Factsheets
guidelines for Europe; p. 23.
Sunyer J et al. Eur Heart J. 2003;24:752

19. OZONE LEAD
Properties Major Constituent of SMOG
Not to be confused with the ozone
in the upper atmosphere
Naturally occurring and does not go
away over time, unlike most
pollutants
Source Reaction with sunlight of
pollutants such as NOx from
vehicle and industry and VOCs
emitted by vehicles, solvents and
industry.
Indoor - Old paint found in homes
built before 1978
Lead contaminated soil and dust
tracked indoors from outside
Outdoor - Burning of leaded petrol
The highest levels occur during
periods of sunny weather
Eliminated lead from gasoline and
paints, significantly reduced lead in air
pollution in the United States, cutting
it by 98% by 2002
AIR POLLUTION:
2: GASEOUS
Glenn BS et al Epidemiology. 2003;14:30–6
Weiss ST et al Am J Epidemiol. 1986;123:800–8

20.  Indoor sources - Poorly installed and maintained heating systems
(angeethi ), charcoal grills, gas kitchen stoves , water heaters
 Outdoor sources - Automobiles, cigarette smoke ,industrial processes,
and burning of fossil fuels
 Harmful effects are more profound in the myocardium than in
peripheral tissues because of very high oxygen extraction
AIR POLLUTION:
2: GASEOUS
CARBON MONOXIDE

22.  Consists of nicotine, tar or particulate phase with many
carcinogens, and gaseous compounds including CO
 Well-established risk factor for CVD
 Smoke from BIDIS contains three to five times the amount of
nicotine as a regular cigarette
Pryor WA, Stone K. Oxidants in cigarette smoke.. Ann N Y Acad Sci. 1993;686:12–28
AIR POLLUTION
3:VOLATILE ORGANIC COMPOUNDS
CIAGARATTE SMOKE

23.  Diesel - Fuel of choice for use in mass transportation vehicles
 Diesel fuel and the products of its combustion represent one of the most common
toxins to which people living in both urban and rural areas of the world
 Majority of these particles found in the greatest concentration within immediate
vicinity of busy streets or highways.
 Components of diesel exhaust
 Carbon monoxide and carbon dioxide
 Nitrogen oxides
 Sulfur oxides
 HYDROCARBONS
 Unburned carbon particles (soot)
Irina N. Krivoshto et al J Am Board Fam Med 2008;21:55– 62
AIR POLLUTION
3:VOLATILE ORGANIC COMPOUNDS
DIESEL EXHAUST

24.  On an equal horsepower basis, diesel exhaust is 100 times more toxic
 Contribute to formation of ambient particulate matter of all sizes,
predominantly harmful Fine fraction and UFP
 Organic compounds from diesel exhaust with known toxic and carcinogenic
properties, such as polycyclic aromatic hydrocarbons (PAH adhere easily to
the surface of the carbon particles and are carried deep into the lungs.
 Toxic compounds in higher concentrations than gasoline engines, including
nitrogen oxides, sulfur oxides, ozone, formaldehyde, benzene
Irina N. Krivoshto et al J Am Board Fam Med 2008;21:55– 62
Zielinska B et al J Air Waste Manag Assoc 2004;54:1138 –50.
AIR POLLUTION
3:VOLATILE ORGANIC COMPOUNDS
DIESEL vs PETROL EXHAUST

25.  Compressed natural gas, or CNG, is natural gas under pressure
which remains clear, odorless, and non-corrosive.
 Natural gas burns cleaner than conventional gasoline or diesel
due to its lower carbon content.
 Natural gas vehicles show an average reduction in ozone-
forming emissions of 80 percent compared to gasoline vehicles
 The emissions of primary concern include the regulated
emissions of hydrocarbons, NOx, CO , CO2
http://www.afdc.energy.gov/
AIR POLLUTION
3:VOLATILE ORGANIC COMPOUNDS
CNG EXHAUST

26. SMOG
 Type of air pollutant
 Coal
 Transportation emissions The major culprits are are CO, NO and NOx, VOCs ,sulfur
dioxide, and hydrocarbons.
These molecules react with sunlight, heat, ammonia, moisture, and other
compounds to form the noxious vapors, ground level ozone to form smog
 Photochemical smog
It is the chemical reaction of sunlight, nitrogen oxides and volatile organic compounds
(VOCs) in the atmosphere
 Natural causes
An erupting volcano can also emit high levels of sulphur dioxide along with a large
quantity of particulate matter; two key components to the creation of smog

27. Pathophysiology of Air
Pollution and CVD

28. 1. INDIRECT PULMONARY-DERIVED
EFFECTS
Li XY et al Thorax 51 ; 1216-122
Van Eeden SF et al. (2001) Am J Respir Crit Care Med 164: 826–830
Seaton A et al Lancet 345 ; 175-178
 Provokes an inflammatory response in the lungs
 Consequent release of prothrombotic and inflammatory cytokines
into the circulation.
 Animal studies have demonstrated pulmonary inflammation after
inhalation of ambient PM and dilute diesel exhaust.
 Lead to elevated plasma cytokines such as interleukin (IL)-1β, IL-6,
and GMCSF
 Evidence of an acute phase response, increased CRP , plasma
fibrinogen, plasma viscosity

29.  Fine PM or UFP could rapidly translocate into the circulation
 Particle translocation seems plausible–either as naked particle or
after ingestion by alveolar macrophage
 Injured arteries are well known to take up blood borne
nanoparticles, a fact exploited by the nanotechnology industry
2. DIRECT TRANSLOCATION INTO
CIRCULATION
Nemmar A et al. (2001). Am J Respir Crit Care Med 164: 1665–1668
Kreyling WG et al. (2002) . J Toxicol Environ Health A 65: 1513–1530
Oberdorster G et al. (2002) J Toxicol Environ Health A 65: 1531–1543

30.  Studied the passage of radioactively labeled ultrafine particles after their
intratracheal instillation.
 Significant fraction of 99mTc-albumin, taken as a model of ultrafine particles,
rapidly diffuses from the lungs into the systemic circulation.
 Pulmonary and peripheral effects of inhaled ultrafine carbon particles in old rats that were
injected with endotoxin (lipopolysaccharide, LPS) to model systemic gram-negative bacterial
infection
 In both strains, ultrafine particles (UFP) were found to decrease the number of blood PMNs,
increase the intracellular oxidation of a fluorescent dye (DCFD) in blood PMNs, and affect
plasma thrombin-anti-thrombin (TAT) complex and fibrinogen levels

31. 3. AUTONOMIC MECHANISM
 Parasympathetic nervous system withdrawal and/or sympathetic
nervous system activation
 PM deposited in the pulmonary tree can directly stimulate lung nerve
reflexes via irritant receptors
 Alter systemic autonomic balance (Change baroreceptor settings)
Robert D Brook Clinical Science 2008

32. 4 .OXIDATIVE STRESS

33. MECHANISM OF DISEASE

34. 1. ATHEROGENESIS
 Repeated exposure to air pollution could induce atherosclerotic plaque
expansion or rupture
 Prolonged exposure to ambient PM2.5 increased aortic plaque area and
burden, compared with filtered air
 In a cross-sectional, population-based study, CIMT measurements in nearly
800 residents of Los Angeles, CA.
 For every 10 g/m3 increase in PM2.5, carotid intima–media thickness increased by 6%
Sun Q et al. JAMA 2005;294:3003–10.
Hoffmann B et al. Circulation 2007;116:489–96
Kunzli N et al. (2005).Environ Health Perspect 113: 201–206

35. 2. ENHANCED THROMBOSIS
 Induce a variety of prothrombotic effects including enhanced expression of TF
and accumulation of fibrin and platelets on ENDOTHELIUM
 Could themselves act as a focus for thrombus formation
 With underlying vulnerable atherosclerotic plaques, the generation of a pro-
thrombotic milieu could trigger arterial thrombosis and subsequent ACS
 Long-term exposure to particulate air pollution linked to an increased risk of
venous thromboembolic disease
Peters, A et al Lancet 349, 1582–1587
Baccarelli A et al. 2008 Arch InternMed 168: 920–927

36. 3. VASCULAR DYSFUNCTION

37. 4. ARRYTHMOGENESIS

38. VENTRICULAR ARRHYTHMIAS
 In a study , 100 patients who had 223 ICD discharges . Higher levels
of NO2 , CO, black carbon, fine particles was associated with
increased defibrillator therapy.
 In another cohort 203 ICD patients followed for mean of 3.1 yrs
with 798 confirmed ventricular arrhythmias showed a linear
exposure response between PM2.5 and ozone and arrhythmias.
 In a study, 211 patients suffered 140 symptomatic ventricular
arrhythmias. There was an association between two-hour moving
averages of PM10 and ventricular arrhythmias
Peters A et al. Epidemiology. 2000
Rich DQ et al Am J Epidemiol. 2005

39. ATRIAL FIBRILLATION
 In sub-analysis of Boston ICD study, there were 900 episodes of
paroxysmal Afib documented by the ICDs
 Statistically significant association between Afibs and increased O3
in the hr before arrhythmia
 Weekly 30 minute Holter for 24 weeks in 32 nonsmoking adults
demonstrated an increased risk of SVTs for 5-day moving averages of
PM2.5, sulfate and ozone
Sarnat SE et al. Occup Environ Med. 2006
Rich DQet al Am J Epidemiol. 2005

40. HEART RATE VARIABILITY
 Putative marker of cardiac autonomic function
 In controlled studies, 76 young healthy students showed decreased HRV
indices associated with increases in levels of PM, sulfate, nitrate, and ozone.
 Acute exposure of elderly individuals with CAD to elevated concentrations of
coarse and fine particles resulted in a decrease in HRV
Chuang KJet al. Am J Respir Crit Care Med. 2007
Lipsett MJ et al. Environ Health Perspect 2006
Tsuji H et al. Circulation 1996

41. MAGNITUDE OF RELATIONSHIP

42. Short-term exposure studies

43. STUDY Source STUDY
TYPE
Exposure
Increment
Percent Increases in RR
Cardiovascular mortality (95% CI)
NMMAPS
(US)
Dominici et al
2003
Time series 20ug/m3
PM10
0.6 (0.3–1.0)
APHEA2
(UK)
Analitis et al
Epidemiology
2006
Time series 20ug/m3
PM10
1.5 (0.9–2.1)
COMEAP COMEAP
2006
Meta
analysis
20ug/m3 PM10
10ug/m3 PM2.5
1.8 (1.4–2.4)
1.4 (0.7–2.2
US, 27
cities
Franklin et al
J Expo Sci Environ
Epidemiol. 2007
Case
crossover
10ug/m3 PM2.5 All Cause Mortality 1.2 (0.3–2.1)
NMMAPS, National Morbidity, Mortality, and Air Pollution Study
APHEA2, Air Pollution and Health: A European Approach 2
COMEAP, Committee on the Medical Effects of Air Pollutant

44. IHCS
Intermountain Heart Collaborative Study
 Case-crossover study design
 Ischemic events in 12 865 patients
 PM2.5 elevated by 10 g/m3 was associated with increased risk of acute
ischemic coronary events (unstable angina and myocardial infarction) equal to
4.5%
 Short-term particulate exposures contributed to acute coronary events,
especially among patients with underlying coronary artery disease
Circulation. 2006;114:2443-2448

45.  Case cross-over study
 691 patients with MI
 An association was found between exposure to traffic and the onset of a
myocardial infarction within one hour afterward (odds ratio, 2.92; 95 % CI 2.22
to 3.83; P<0.001).
 The time the subjects spent in cars, on public transportation, or on motorcycles
or bicycles was consistently linked with an increase in the risk
 Adjusting for the level of exercise on a bicycle or for getting up in the morning
changed the estimated effect of exposure to traffic only slightly (odds ratio
f2.73; 95 % CI interval, 2.06 to 3.61; P<0.001).
 The subject’s use of a car was the most common source of exposure to traffic
 There was also an association between time spent on public transportation

48. Long-term exposure studies

49.  WeCohort survival analysis
 Cohort Survival Analysis
 Annual city-specific PM2.5 concentrations were measured between
1979 and 1988, and estimated for later years from publicly available
data
 Found an increase in overall mortality associated with each 10 g/m3
increase in PM2.5 (RR, 1.16; 95% CI, 1.07–1.26] and cardiovascular
deaths (RR,1.28;95% CI, 1.13–1.44).
 Improved overall mortality was associated with decreased mean
PM2.5 (10 g/m3) between periods (RR, 0.73; 95% CI, 0.57–0.95)

51.  Cohort survival analysis
 The extended 16-year follow-up in approx. 5,00, 000 adults
demonstrated a 12 % increase in risk for death from CV causes
per 10 μg/m3 increase in long-term PM2.5 exposure.
 Death from ischaemic heart disease (18 % increase) was the
single largest cause of mortality
 Larger risks being observed for smokers relative to nonsmokers.
 Mortality attributable to respiratory disease had relatively weak
associations.

52. Cardiovascular mortality in
long term exposure studies
Associated with increments of 10 µg/m3 PM2.5
Pope and Dockery, 2006, JAWMA, 56(6)

54.  1,00,166 people were enrolled from 1997 to 2007 and followed for an
average of 11.5 years
 5157 participants experienced incident events.
 A 5 μg/m3 increase in estimated annual mean PM2.5 was associated with a
13% increased risk of coronary events (hazard ratio 1.13, 95% confidence
interval 0.98 to 1.30)
 10μg/m3 increase in estimated annual mean PM10was associated with a
12%increased risk of coronary events (1.12, 1.01to1.25)
 Positive associations were detected below the current annual European limit
value of 25 μg/m3 for PM2.5 and below 40 μg/m3 for PM10

55. ARE ALL PEOPLE EQUALLY
SUSCEPTIBLE ?
 Susceptible populations include elderly subjects, diabetic patients
,and individuals with known coronary artery disease
 Obesity and female sex have also been proposed as possible
susceptibility factors
 Many different polymorphisms in various genes, particularly those in
oxidative and inflammatory pathways : proposed to modulate PM-
related cardiovascular outcome
Brook RD, et al. Circulation 2010;121:2331–78
Miller KA et al.N Engl J Med 2007;356:447–58.

56. AIR POLLUTION IN INDIA
Source HT 2012 OCT

57. AIR POLLUTION IN DELHI

59. AIR POLLUTION IN DELHI
Source : INDIA TODAY 2013

61. HT JAN 2014

62. PHARMACOLOGICAL THERAPY
 Noticeable deficit in studies
 Few epidemiological studies have suggested that use of statins or β-
blocker drugs can limit the effects of PM
 Done in specific populations and with limited end points investigated
 Useful to consider whether current medical therapies may be useful
adjunct intervention
Schwartz J et al Am. J. Respir. Crit. Care Med (2005)
Pekkanen. Circulation 106(8), 933–938 (2002

63. ANTIOXIDANTS
 Strong evidence from animal models that a range of antioxidant
compounds can prevent the effects of PM both in vitro and in vivo
 No evidence in man , just a reflection of the difficulty in studying
oxidative stress in man
 Enthusiasm for such an approach is dented by the poor outcome data
from clinical trials
Cheng YW, Kang JJ. J. Toxicol. Environ. Health A 57(2)(1999)
Nemmar AS et al Toxicology 263(2–3), 84–92 2009

64. PREVENTIVE MEASURES
 Plan your activities when and where pollution levels are lower
 Reduce your overall risk of heart disease or stroke
 Know when and where particle and ozone pollution levels may be
unhealthy
 When masks are used, they should be N95 or P100 mask respirators
that effectively remove very small air pollution particles

65.  Acknowledged air pollution is a serious concern with severe public health
consequences
 Delhi has lost CNG gains: Need urgent action
 CNG pricing is a risk to CNG programme
 Poor emission standards
 Diesel price equalization with petrol or tax on diesel cars
 Right to safe walk and cycling on all roads
 Every hour one person is either killed or injured in road accident in Delhi.
 Implementation of daily air quality alert with health advisory

66. SUMMARY
 Epidemiological evidences supports the detrimental role of PM on
cardiovascular morbidity and mortality
 Strongest evidence is with PM (100 times more in diesel exhaust )
 Increased risk is predominantly confined to susceptible individuals
 Mechanism involved autonomic function , direct translocation and systemic
oxidative stress with inflammation

67. SUMMARY
 Day has come to routinely ask patients about exposure to air pollutants?
(Risk factor )
 All CVD patients should be educated about adverse effect of Air Pollution
 Air pollution in Delhi have risen markedly making it the world’s most
polluted city
 Time for formation of strong policies and their implementation and adopt
measures to reduce air pollution as a public health priority.

69. We will breathe easier when the air in community is clean and healthy
We will breathe easier when people are free from the addictive grip of
cigarettes and the debilitating effects of lung disease
We will breathe easier when the air in our public spaces and workplaces are
clear of second hand smoke
Until then, we are fighting for air
Time to reclaim the air we breathe

71. VASCULAR DYSFUNCTION

74. The time course and numerous ways inhaled particulate matter alters cardiovascular function

77. MECHANISMS OF DISEASE

80. ANTIOXIDANTS – FUTURE
PRESPECTIVE
 Need for better-designed antioxidant therapies that have the capacity to
specifically reach the locations under attack from the oxidative actions of PM
 Antioxidants that can be readily recycled to replenish key endogenous
antioxidant pools.
 Other classes of pharmacological agents, for those that inhibit enzymatic
sources of free radicals activated by PM (e.g., NADPH oxidase)
 block the sensory receptors in the lung that could mediate the cardiovascular
effects of PM via the autonomic nervous system.

81. air space epithelial permeability was assessed as the total protein in BAL
fluid in vivo. The oxidant properties of PM10 particles were determined by
their ability to cause damage to plasmid DNA and by changes in reduced
(GSH) and oxidised (GSSG) glutathione. The effects of PM10 particles were
compared in some experiments with those of fine (CB) and ultrafine (ufCB)
carbon black particles. RESULTS: Six hours after intratracheal instillation of
PM10 there was an influx of neutrophils (up to 15% of total cells in BAL fluid)
into the alveolar space, increased epithelial permeability, the mean (SE)
total protein in the BAL fluid increasing from 0.39 (0.01) to 0.62 (0.01)
mg/ml, and increased lactate dehydrogenase (LDH) concentrations in the
BAL fluid. An even greater inflammatory response was seen following
intratracheal instillation of ufCB but not following CB instillation. PM10
particles had free radical activity in vivo, as shown by a decrease in GSH
levels in the BAL fluid from 0.36 (0.05) to 0.25 (0.01) nmol/ml following
instillation. The free radical activity of PM10 was confirmed in vitro by its
ability to deplete supercoiled plasmid DNA, an effect which could be
reversed by mannitol, a specific hydroxyl radical scavenger. BAL fluid
leucocytes from rats treated with PM10 produced greater amounts of nitric
oxide (NO), measured as nitrite (control 3.07 (0.33), treated 4.45 (0.23)
microM/1 x 10(6) cells), and tumour necrosis factor alpha (control 21.0
(3.1), treated 179.2 (29.4) units/l x 10(6) cells) in culture than those
obtained from control animals. Since the PM10 preparation was
contaminated with small amounts of filter fibres due to the extraction
process, the effects of instillation of filter fibres alone was assessed. These
studies showed that filter fibres did not account for the proinflammatory and

87. STUDY YEAR Type of Analysis RESULTS
Harvard Six Cities
(extended analysis)
2006 Cohort survival analysis The extended 28-year follow-up in approx.
8096 people living in U.S. showed that the
RR for CV death was increased significantly
by 1.28 per 10 μg/m3 increase in long-term
PM2.5.
The decrease in PM2.5 over the
study period resulted in a significant
reduction in CV mortality (relative risk of
0.69).
American Cancer
Society II (extended
analysis)
2004 The extended 16-year follow-up in approx.
500 000 adults demonstrated a 12 %
increase in risk for death from CV causes
per 10 μg/m3 increase in long-term PM2.5
exposure.
Death from ischaemic heart disease (18 %
increase) was the single largest cause of
mortality, with smaller absolute numbers
ofpeople (although with similar relative risk
elevations) dying from arrhythmias and
heart failure.

88. ATHEROGENESIS
 In a cross-sectional, population-based study, Künzli and colleagues examined
CIMT measurements in nearly 800 patients
 For every 10 μg/m3 increase in PM2.5, CIMT by 6%, which fell to 4% after
adjustment for confounding variables
Plos One 2010

90. Fine particulate matter (PM2.5)
 Sources of PM2.5 - Both outdoor and indoor sources of fine particulates (PM with an
aerodynamic diameter less than 2.5 μm [PM2.5]).
 Particles in the PM2.5 size range are commonly found in smoke and haze and are of
particular health concern since they are able to travel deeply into the respiratory tract,
reaching the lungs and can also affect the heart.
Human combustion of fossil fuels from different outdoor activities, such as from car, truck,
bus, and off-road vehicle (e.g., construction equipment, snowmobile, locomotive) exhausts,
other operations that involve the burning of fuels such as wood, heating oil, or coal, as well as
natural sources such as forest and grass fires
 Common indoor activities, and such indoor sources of fine particles include tobacco smoke,
cooking (e.g., frying, sautéing, and broiling), burning candles or oil lamps, and operating
fireplaces and fuel-burning space heaters (e.g., kerosene heaters).
 Fine particles can also be emitted from the reaction of gases or droplets in the atmosphere
from sources such as power generation plants.